Unveiling Global Human Trafficking Trends: A Comprehensive Analysis

This paper presents a comprehensive analysis of global human trafficking trends over a twenty-year period, leveraging a robust dataset from the Counter Trafficking Data Collaborative (CTDC). The study unfolds in a systematic manner, beginning with a detailed data collection phase, where ethical and legal standards for data usage and privacy are strictly observed. Following collection, the data undergoes a rigorous preprocessing stage, involving cleaning, integration, transformation, and normalization to ensure accuracy and consistency for analysis. The analytical phase employs time-series analysis to delineate historical trends and utilizes predictive modeling to forecast future trajectories of human trafficking using the advanced analytical capabilities of Power BI. A comparative analysis across regions—Africa, the Americas, Asia, and Europe—is conducted to identify and visualize the distribution of human trafficking, dissecting the data by victim demographics, types of exploitation, and duration of victimization. The findings of this study not only offer a descriptive and predictive outlook on trafficking patterns but also provide insights into the regional nuances that influence these trends. The article underscores the prevalence and persistence of human trafficking, identifies factors contributing to its evolution, and discusses the implications for policy and law enforcement. By integrating a methodological approach with quantitative analysis, this research contributes to the strategic planning and resource allocation for combating human trafficking. It highlights the necessity for continued research and international cooperation to effectively address and mitigate this global issue. The implications of this research are significant, offering actionable insights for policymakers, law enforcement, and advocates in the ongoing battle against human trafficking.

The role of Arabidopsis 5PTase13 in root gravitropism through modulation of vesicle trafficking

Inositol polyphosphate 5-phosphatases （5PTases） are enzymes of phosphatidylinositol metabolism that affect various aspects of plant growth and development. Arabidopsis 5PTasel3 regulates auxin homeostasis and hormonerelated cotyledon vein development, and here we demonstrate that its knockout mutant 5pt13 has elevated sensitivity to gravistimulation in root gravitropic responses. The altered responses of 5pt13 mutants to 1-N-naphthylphthalamic acid （an auxin transport inhibitor） indicate that 5PTase13 might be involved in the regulation of auxin transport. Indeed, the auxin efflux carrier PIN2 is expressed more broadly under 5PTasel3 deficiency, and observations of the internalization of the membrane-selective dye FM4-64 reveal altered vesicle trafficking in 5pt13 mutants. Compared with wild-type, 5pt13 mutant seedlings are less sensitive to the inhibition by brefeldin A of vesicle cycling, seedling growth, and the intracellular cycling of the PIN1 and PIN2 proteins. Further, auxin redistribution upon gravitropic stimulation is stimulated under 5PTasel3 deficiency. These results suggest that 5PTasel3 may modulate auxin transport by regulating vesicle trafficking and thereby play a role in root gravitropism.

Modulation of cell surface GABA B receptors by desensitization,trafficking and regulated degradation

Inhibitory neurotransmission ensures normal brain function by counteracting and integrating excitatory activity.-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the mammalian central nervous system,and mediates its effects via two classes of receptors:the GABA A and GABA B receptors.GABA A receptors are heteropentameric GABA-gated chloride channels and responsible for fast inhibitory neurotransmission.GABA B receptors are heterodimeric G protein coupled receptors (GPCR) that mediate slow and prolonged inhibitory transmission.The extent of inhibitory neurotransmission is determined by a variety of factors,such as the degree of transmitter release and changes in receptor activity by posttranslational modifications (e.g.,phosphorylation),as well as by the number of receptors present in the plasma membrane available for signal transduction.The level of GABA B receptors at the cell surface critically depends on the residence time at the cell surface and finally the rates of endocytosis and degradation.In this review we focus primarily on recent advances in the understanding of trafficking mechanisms that determine the expression level of GABA B receptors in the plasma membrane,and thereby signaling strength.

Important relationships between Rab and MICAL proteins in endocytic trafficking

The internalization of essential nutrients,lipids and receptors is a crucial process for all eukaryotic cells.Accordingly,endocytosis is highly conserved across cell types and species.Once internalized,small cargocontaining vesicles fuse with early endosomes(also known as sorting endosomes),where they undergo segregation to distinct membrane regions and are sorted and transported on through the endocytic pathway.Although the mechanisms that regulate this sorting are still poorly understood,some receptors are directed to late endosomes and lysosomes for degradation,whereas other receptors are recycled back to the plasma membrane;either directly or through recycling endosomes.The Rab family of small GTP-binding proteins plays crucial roles in regulating these trafficking pathways.Rabs cycle from inactive GDP-bound cytoplasmic proteins to active GTP-bound membraneassociated proteins,as a consequence of the activity of multiple specific GTPase-activating proteins(GAPs) and GTP exchange factors(GEFs).Once bound to GTP,Rabs interact with a multitude of effector proteins that carry out Rab-specific functions.Recent studies have shown that some of these effectors are also interaction partners for the C-terminal Eps15 homology(EHD) proteins,which are also intimately involved in endocytic regulation.A particularly interesting example of common Rab-EHD interaction partners is the MICALlike protein,MICAL-L1.MICAL-L1 and its homolog,MICAL-L2,belong to the larger MICAL family of proteins,and both have been directly implicated in regulating endocytic recycling of cell surface receptors and junctional proteins,as well as controlling cytoskeletal rearrangement and neurite outgrowth.In this review,we summarize the functional roles of MICAL and Rab proteins,and focus on the significance of their interactions and the implications for endocytic transport.

Luminal/extracellular domains of chimeric CI-M6PR-C proteins interfere with their retrograde endosome-to-TGN trafficking in the transient expression system

The membrane trafficking of cation-independent mannose 6-phosphate receptor（CI-M6PR） between the transGolgi network（TGN） and endosomal compartments is not only critical for maintaining lysosomal function but also a well-known event for understanding molecular and cellular mechanisms in retrograde endosome-to-TGN trafficking.Although it has been well established in literature that the C-terminus of bovine CI-M6PR determines its retrograde trafficking,it remains unclear whether the luminal domain of the protein plays a role on these sorting events.In this study,we found that partial deletion of luminal domain of human CI-M6PR mistargeted the mutant protein to nonTGN compartments.Moreover,replacing the luminal domain of both bovine and human CI-M6PR with that from irrelevant membrane proteins such as CD8 or Tac also altered the TGN targeting of the chimeric proteins.On the other hand,only short sequence from HA fused with the transmembrane domain and C-terminus of the receptor,HA-hCIM6PR-tail,resulted in its preferential targeting to TGN as for the full length receptor,strongly suggesting that sorting of the receptor may be influenced by luminal sequence.Furthermore,using this luminal truncated form of HA-hCIM6 PR as a model cargo,we found that the trafficking of the chimeric protein was regulated by the retromer complex through interacting with SNX5.In conclusion,our study strongly suggested that the disrupted luminal domain from hCI-M6PR or other irrelevant membrane proteins interfere with the process of membrane trafficking and TGN targeting of CI-M6PR.

Retrograde trafficking of VMAT2 and its role in protein stability in non-neuronal cells

Increasing evidence suggests that the impaired neuroprotection of vesicular monoamine transporter 2（VMAT2）contributes to the pathogenesis of Parkinson＇s disease.That has been linked to aberrant subcellular retrograde trafficking as strongly indicated by recent genomic studies on familial Parkinson＇s diseases.However,whether VMAT2 function is regulated by retrograde trafficking is unknown.By using biochemistry and cell biology approaches,we have shown that VMAT2 was stringently localized to the trans-Golgi network and underwent retrograde trafficking in non-neuronal cells.The transporter also interacted with the key component of retromer,Vps35,biochemically and subcellularly.Using specific siRNA,we further showed that Vps35 depletion altered subcellular localization of VMAT2.Moreover,siRNA-mediated Vps35 knockdown also decreased the stability of VMAT2 as demonstrated by the reduced half-life.Thus,our work suggested that altered vesicular trafficking of VMAT2 may play a vital role in neuroprotection of the transporter as well as in the pathogenesis of Parkinson＇s disease.

Distinctive roles of Rac1 and Rab29 in LRRK2 mediated membrane trafficking and neurite outgrowth

Parkinson＇s disease（PD） associated leucine-rich repeat kinase 2（LRRK2） mutants have shown pathogenic effects on a variety of subcellular processes. Two small GTPases Rac1 and Rab29 have been indicated as possible downstream effectors participating in LRRK2 signaling but their detail mechanisms remain unclear. In this study, we have used biochemical and cell biology approaches to address whether two GTPases interact with LRRK2 and hence function differently in LRRK2 mediated pathogenesis. Here we show that Rac1 and Rab29 specifically interact with LRRK2 with higher affinity for Rab29 and with different preference in functional domain binding. Mutant Rab29 but not Racl alters the endosome-to-TGN retrograde trafficking of a cargo protein cation-independent mannose-6-phosphate receptor（CI-M6 PR） and its stability. On the other hand, overexpressed wild type Rab29 but not Racl rescued the altered retrograde membrane trafficking induced by the pathogenic mutant LRRK2^（G2019 S）. Furthermore,both Rac1 and Rab29 rescued neurite shortening in differentiated SH-SY5 Y cells induced by LRRK2^（G2019 S）. Our study strongly suggests that Rac1 and Rab29 are involved in distinct functions as downstream effectors in LRRK2 signaling pathways.

Structural determinants specific for retromer protein sorting nexin 5 in regulating subcellular retrograde membrane trafficking

The endosomal trafficking of signaling membrane proteins, such as receptors, transporters and channels, is mediated by the retromer-mediated sorting machinery, composed of a cargo-selective vacuolar protein sorting trimer and a membrane-deforming subunit of sorting nexin proteins. Recent studies have shown that the isoforms, sorting nexin 5 (SNX5) and SNX6, have played distinctive regulatory roles in retrograde membrane trafficking. However, the molecular insight determined functional differences within the proteins remains unclear. We reported that SNX5 and SNX6 had distinct binding affinity to the cargo protein vesicular monoamine transporter 2 (VMAT2). SNX5, but not SNX6, specifically interacted with VMAT2 through the Phox domain, which contains an alpha-helix binding motif. Using chimeric mutagenesis, we identified that several key residues within this domain were unique in SNX5, but not SNX6, and played an auxiliary role in its binding to VMAT2. Importantly, we generated a set of mutant SNX6, in which the corresponding key residues were mutated to those in SNX5. In addition to the gain in binding affinity to VMAT2, their overexpression functionally rescued the altered retrograde trafficking of VMAT2 induced by siRNA-mediated depletion of SNX5. These data strongly suggest that SNX5 and SNX6 have different functions in retrograde membrane trafficking, which is determined by the different structural elements within the Phox domain of two proteins. Our work provides a new information on the role of SNX5 and SNX6 in the molecular regulation of retrograde membrane trafficking and vesicular membrane targeting in monoamine neurotransmission and neurological diseases.

Diazepam reduces synaptic GABA type areceptor availability via multiple trafficking mechanisms

OBJECTIVE Investigate the effects of diazepam(DZP) on γ2 subunit containing GABA type A receptor(GABA A R) trafficking.METHODS Immunofluorescence microscopy measured surface GABA A Rs and gephyrin in rat cortical neurons after 24 h exposure of 1.0 μmol·L^(-1) DZP.Biochemical studies of mice injected with 10 mg·kg^(-1) DZP vs vehicle were assessed for γ2 subunit and total gephyrin cortical levels 12 h post-injection.Ubiquitination of the γ2 subunit was studied by immunoprecipitation after 12 h of 1.0 μmol·L^(-1) DZP exposure.A γ2 subunit encoding an N terminal fluorogen-activating peptide and pH-sensitive green fluorescent protein(γ2 pH FAP) measured lysosomal targeting of γ2 containing GABA A Rs.RFP-gephyrin and γ2 pH FAP synaptic diffusion rates were examined using fluorescence recovery after photobleaching(FRAP).RESULTS Extrasynaptic levels of γ2 GABA A Rs decreased by 12.2%,while synaptic gephyrin S270 phosphorylation increased by 18.3% in DZP-treated neurons after 24 h compared to control(P<0.05).Dendritic levels of gephyrin were also reduced to 74.1% of control,while S270 phosphorylation was elevated by 25.2%(P<0.05;P<0.01).Mice 12 h post-DZP injection demonstrated a 12.7% and 26.1% decrease in total γ2 and gephyrin levels,respectively(P<0.05;P<0.01).12 h DZP treatment enhanced γ2 subunit ubiquitination 1.13-fold relative to control(P<0.05).Internalized γ2 pH FAP GABA A Rs associated with lysosomes was 8.0% higher in neurons treated with 12-16 h DZP compared to control.Pilot FRAP experiments suggest gephyrin and γ2 have increased mobility and turnover at synapses following DZP.CONCLUSION DZP treatment decreases γ2 GABA A R levels and gephyrin scaffolding function after one day of exposure,which may contribute to the formation of DZP tolerance.

Effects of Human Trafficking on Household Farm Labor Availability Among Arable Farming Households in Delta State,Nigeria

Trafficking in persons, especially women and girls has been on for long and is still going on. Persons in the female group constitute the mostly trafficked humans. This study was conducted to determine the effects of human trafficking on household farm labor needs available among farming households. Arable farming households involved in human trafficking were identified and purposively selected for this study with the aid of key informants in purposively selected communities. This led to the selection of 60 arable farming household heads in Delta North Agricultural zone, 65 farming household heads in Delta Central Agricultural Zone, and 36 arable farming household heads in Delta south agricultural zone to give a total of 151 respondents. Data for the study were collected with the utilization of questionnaire and interview schedule. The collected data were subjected to statistical analysis with the application of frequency counts, percentages and means derived from 4-point likert-type scale. The hypothesis was tested using Tobit regression analysis. Human trafficking was found to be age and sex selective and the causes of human trafficking included both push and pull factors, such as high income in destination countries poverty, low risk profit, nature of trafficking in persons, ease in control and manipulation of vulnerable women and girls, low risk involved in working in destination countries, lacking of legitimate and fulfilling employment, sex selective migration policies, less access to information and peer pressure. Shortage of household farm labor was experienced by farming households in clearing and brushing of farm land, sowing, weeding, harvesting and processing/storage. Human trafficking was found to affect household labor availability in clearing/brushing of farm land, sowing, weeding, harvesting and processing/storage of farm produce. It is recommended that poverty alleviation programs should be specially organized for poor women, government and NGOs and international agencies should develop strategies to mitigate human trafficking. The government needs to collaborate with community based organizations and law enforcement agencies to create anti-trafficking committee in fanning communities. Community education should be created for the farming communities to emphasize anti-human trafficking with the use of change agents; extension agents should integrate anti-trafficking messages in their interaction with farmers.

Drug Trafficking and Propaganda: The Image of Drug Trafficking in the Mexican Press 2006-2010

The aim of this study is to identify and analyze the pattern of visibility of the main actors in the photographic coverage of drug trafficking in six of Mexico’s national newspapers. The study was based on a sample of 12,962,000 photographs published from 2006 to 2010. The images were processed by generating a codebook of key categories extracted from the informational context of drug trafficking and the war against drug trafficking. The technique used to explain the newspapers’ photographic coverage was the content analysis proposed by Johan Galtung in 1965, in its updated version of 2006. The limitations of the research are time constraints (only four years of President Felipe Calderón’s six-year term were analyzed) and information platforms (with the omission of online newspapers, supplements, and additional publications). The study offers an original analysis of the photographic coverage of drug trafficking in the Mexican press. The use of the Galtung Model reveals strong biases and imbalances in the coverage, with a clear tendency to defend the government’s position in the analyzed sample.

Sex Slavery in India： Unpacking the Stories of Trafficking Victims

While there is no consensus on the number of domestic sex trafficking victims in India, the phenomenon is estimated to be widespread and the evidence of its impact on victims is devastating. This paper explored the narratives of 10 sex trafficked women from a major non-government organization in New Delhi. Qualitative methodology was adopted and data were collected through open-ended unstructured interviews. The victimological paradigm including the Lifestyle Risk Model （LRM） by Van der Hoven and Maree provided the framework to discuss the key issues related to sex trafficking. Psychological experiences such as being abused by husbands, and in some cases, victims＇ own families; social conditions such as poverty and education; cultural practices such as vulnerability of women and marginalization; and lifestyle risk factors were observed throughout the stories of the victims. Furthermore, shame was found to be the core emotion in the stigmatization process. Limitations and future directions are also discussed.

ssues of Human Beings Trafficking in Albania

The theme of trafficking of human beings treats one of the most severe and dangerous criminal phenomena of the organized crime in Albania. The objects of this paper are： human trafficking; ways of trafficking; risk of Albanian society; and investment of the criminal benefits deriving from trafficking in legal economic activities, it is of great importance for the treatment of proactive investigations to the trafficking of human beings. Another important aspect of the trafficking investigations is the investigation of criminal assets and the way how they are used in the economy of the country. In this paper, we stress that the investigation of criminal assets benefited by the crime of trafficking human beings as well as other wealth financed by these assets is important as the investigation of the criminal activity of trafficking itself. Also, we aim to evaluate the necessity of acting of all law enforcement agencies and other state institutions in order to be successful in the fight against the crime of trafficking of human beings. At the end of this paper, we do treat the necessity and the ways of collaboration of law enforcement agencies, NGOs, and structures of local government for rehabilitation of the victims of trafficking and their integration in the social life.

Training for Tourism Companies Staff Against Human Trafficking

Human trafficking, involving mostly women and children, is closely related to the tourism businesses, because traffickers use often through their complicity, which including various companies： airports, trains, hotels, etc.. This work1 aims to analyze the effectiveness of training as a tool for monitoring and preventing this crime. After data and information collecting on the issue of human trafficking and links with the tourism industry, we analyzed the main training toolkits provided by organizations which deal with the prevention and monitoring of this phenomenon, two questionnaires were built and sent： the first questionnaire was sent to 136 organizations that are training for the staff of tourism companies; it aims to detect the educational needs that the organizations want to satisfy, the educational target, teaching techniques, and the results obtained with the training; the second questionnaire was sent to 495 companies who participating in the courses, explores the motivations, the educational objectives, and results related to the training received. Through this work, the authors only present the first results obtained during the first phase, involving the point of view of seven organizations offering training courses. The answers provided by the companies show that the learning targets have been fully achieved, in particular with regard to raising awareness on the issue. Still, some gaps with regard to the support that the training may offer in the development of new attitudes and skills to prevent and monitor the phenomenon. The course contents and teaching techniques used appear to be consistent with the objectives. All of the organizations interviewed carried out the evaluation of the course learning demonstrate how companies training participants are satisfied with the results, especially in terms of knowledge and skills to contribute to the prevention of an increasing phenomenon, while less significant are the advantages about the decrease of concrete human trafficking situations.

Human Smuggling and the International Sex Trade： An Evaluation of the Trafficking Victims Protection Act

The United States Congress set a benchmark in US anti-human trafficking policy with the Trafficking Victims Protection Act of 2000 （TVPA 2000J. The TVPA 2000 and its subsequent reauthorizations in 2003, 2005, and 2008 were put forth to increase the scope, focus, and effectiveness of US efforts to combat human trafficking. In-depth analyses of each reauthorization provide an understanding of the aims of the TVPA. The evolution of the TVPA reauthorizations dearly demonstrates that the US is committed to thwarting human trafficking both domestically and internationally. The analyses examine strengths and weaknesses of the legislation and provide insight as to how the TVPA reached its current state as the William Wilberforce Trafficking Victims Protection Reauthorization Act of 2008 （TVPRA 2008）. Drawing from the evolution of TVPA legislation, the future of the human trafficking phenomenon and legislation is discussed.

Fight Cross-border Trafficking of Women

A boat full of Vietnamese women sails across Beilunhe River which borders China and Vietnam. The women come to the Chinese side for a day's trade before turning back home at 5:00 pm. The border river Beilunhe River could narrow to some 20 meters when the tide ebbs low.

Ethical and policy considerations for organ trafficking and transplant tourism:Based on the UK's first international case of human trafficking for the purpose of organ removal

This study examines the UK's May 2023 judgment in an international organ trafficking and organ tourism case.Human trafficking for organ removal is one of the least understood but growing forms of trafficking worldwide.Countries in the Middle East,Asia,and the Americas are often widely criticized by the international transplant community as sites for organ trafficking.However,we believe that when discussing this issue,it is not just these areas that need to be addressed.What is particularly special is that this case not only involves transnational human trafficking,organ trafficking,and illegal organ transplantation interest chains but also involves the participation of national political officials and complex social and humanistic factors.This article focuses on the current ethical and policy issues involved in organ transplant tourism and organ trafficking and analyzes the implications of this case for our country's donation and transplantation work.

Human trafficking risk factors,health impacts,and opportunities for intervention in Uganda:a qualitative analysis

Background Human trafficking is a global public health issue that is associated with serious short-and long-term morbidity.To address and prevent human trafficking,vulnerabilities to human trafficking and forces sustaining it need to be better understood among specific subpopulations.We aimed to explore risk and protective factors for human trafficking,the health impact of exploitation,and barriers and facilitators of seeking help throughout the human trafficking trajectory among forced labor and sex trafficking victims in Kampala,Uganda.Methods Between March and November 2020,in-depth,semi-structured qualitative interviews were conducted with 108 victims of forced labor and sex trafficking who had completed a human trafficking survey conducted by the Uganda Youth Development Link(UYDEL).Participants who experienced various forms of exploitation were purposively invited for qualitative interviews and a convenience sample was interviewed.Interviews explored personal history,trafficking recruitment,experiences of exploitation and abuse,and experiences seeking help.Interviews were analyzed using a combination of deductive and inductive thematic analysis.Themes and subthemes were organized using an adapted conceptual framework of human trafficking.Results Poverty and an abusive home life,frequently triggered by the death of a caretaker,underpinned vulnerability to human trafficking recruitment.Limited education,lack of social support,and survival needs pushed victims into exploitative situations.Victims of human trafficking were systematically exploited and exposed to dangerous working conditions.Victims suffered from sexually transmitted diseases,incontinence,traumatic fistulae,musculoskeletal injuries,and mental health symptoms.Lack of awareness of resources,fear of negative consequences,restrictions on movement,and dependence on the trafficker and exploitation income prevented victims from seeking help.The police and healthcare workers were the few professionals that they interacted with,but these interactions were oftentimes negative experiences.Conclusions To address and prevent human trafficking,localized interventions are needed at all stages of the human trafficking trajectory.Health impacts of human trafficking are severe.As some of the few professionals trafficking victims interact with,police and healthcare workers are important targets for anti-trafficking training.Improved understanding of human trafficking drivers and barriers and facilitators to seeking help can inform the design of necessary interventions.

Trafficking of Vietnamese women and girls for marriage in China

Background:Bride-trafficking has been a growing phenomenon in Southeast Asia,particularly in China,where one-child policies have resulted in demographic imbalances favoring males.Yet,empirical evidence about women and girls sold into marriage in China remains sparse.Methods:This study describes the experiences of 51 Vietnamese women and girls as young as 14 in post-trafficking services who were sold into marriage in China.A consecutive sample of individuals from five services in Vietnam were invited to be interviewed within the first 2 weeks of admission.It is part of a wider dataset for research on the health of men,women,and children in post-trafficking services in Cambodia,Thailand,and Vietnam,the largest study to date on human trafficking and health.We calculated proportions for all variables and conducted bivariate analyses using Fisher Exact Tests for their associations with mental health disorders symptoms.Results:Before leaving home,31%(n=15)participants were married.Participants reported high levels of sexual violence(n=43;86%)while trafficked and59%(n=30)spent time in detention before returning to Vietnam.Once in post-trafficking care 52.9%(n=27)reported probable depression,anxiety or post-traumatic stress disorders(PTSD),two women(4%)attempted suicide in the past month and 38(75%)remained afraid of their trafficker.Ten(22%)became pregnant while trafficked,and seven(16%)were pregnant at the interview.Conclusions:The cross-border bride trade between Vietnam and China raises complex policy issues,including questions about detention and immigration rights and strategies for supported return processes,including maternal and child health services.As the repercussions of China’s absent female population will persist,Vietnam and China must grapple with the political and social conditions to implement prevention strategies,and resources for women who fall prey to this cross-border bride trade.

ANP impairs the dose-dependent stimulatory effect of ANG II or AVP on H^(+)-ATPase subcellular vesicle trafficking

The effect of angiotensin II (ANG II) or arginine vasopressin (AVP) alone or plus atrial natriuretic peptide (ANP) on H+-ATPase subcellular vesicle trafficking was investigated in MDCK cells following intracellular pH (pHi) acidification by exposure to20 mMNH4Cl for 2 min in a Na+-free solution containing Schering 28080, conditions under which H+-AT-Pase is the only cell mechanism for pHi recovery. Using the acridine orange fluorescent probe (5mM) and confocal microscopy, the vesicle movement was quantified by determining, for each experimental group, the mean slope of the line indicating the changes in apical/basolateral fluorescence density ratio over time during the first 5.30 min of the pHi recovery period. Under the control conditions, the mean slope was 0.079 ± 0.0033 min-1 (14) and it increased significantly with ANG II [10-12 and 10-7 M, respectively to 0.322 ± 0.038 min-1 (13) and 0.578 ± 0.061 min-1 (12)] or AVP [10-12 and 10-6 M, respectively to 0.301 ± 0.018 min-1 (12) and 0.687 ± 0.049 min-1 (11)]. However, in presence of ANP (10-6 M, decreases cytosolic free calcium), dimethyl-BAPTA/AM (5 × 10-5 M, chelates intracellular calcium) or colchicine (10-5 M, 2-h preincubation;inhibits microtubule-dependent vesicular trafficking) alone or plus ANG II or AVP the mean slopes were similar to the control values, indicating that such agents blocked the stimulatory effect of ANG II or AVP on vesicle trafficking. The results suggest that the pathway responsible for the increase in cytosolic free calcium and the microtu-bule-dependent vesicular trafficking are involved in this hormonal stimulating effect. Whether cytosolic free calcium reduction represents an important direct mechanism for ANP impairs the dose-dependent stimulatory effect of ANG II or AVP on H+-ATPase subcellular vesicle trafficking, or is a side effect of other signaling pathways which will require additional studies.