Endothelin and neonatal capsaicin regulate gastric resistance to injury in BDL rats

AIM: To investigate the relationship between primary afferent neurons, endothelin (ET) and the role of its receptors on ethanol-induced gastric damage in cirrhotic rats. METHODS: Cirrhosis and portal hypertension were induced in rats by bile duct ligation (BDL) while controls had a sham operation. The association between ET and afferent neurons on the gastric mucosa was evaluated by capsaicin treatment in newborn rats, the use of ET agonists or antagonists, gastric ET-1 and -3 mRNA and synthetic capacity. Ethanol-induced damage was assessed using ex vivo gastric chamber experiments.Gastric blood flow was measured by laser-Doppler flow-metry. RESULTS: ET-3 and an ETB receptor antagonist sig- nificantly reduced the extent of ethanol-induced gastric damage in BDL rats. Gastric ET-1 and -3 levels were 30% higher in BDL rats compared to control rats. Cap-saicin treatment restored the gastric resistance and blood flow responses to topical application of ethanol in BDL rats and ET-1 and -3 production to levels observed in controls. CONCLUSION: Our results suggest that the reduced resistance of the gastric mucosa of cirrhotic rats to ethanol-induced injury is a phenomenon modulated by ET through the ET B receptor and by sensory afferent neurons.

EFFECT OF FK224 ON THE BRONCHOCONSTRIC TIONINDUCED BY ISOCAPNIC HYPERPNEA IN GUINEA PIGS

Objective To evaluate effect of Neurokinin receptor antagonist on the prevention from hyper-pnea-induced bronchoconstriction using a dual Neurokinin receptor antagonist FK224. Methods 12 pathogen-free Hartley guinea pigs were divided into two groups randomly-. Dimethyl sulfoxide (DMSO) control group (n =6)and FK224 group (n =6). Guinea pigs were anesthetized with pentobarbital sodium. A cervical tracheostomy wasperformed and a polyethylene tube was inserted into the trachea. After measuring baseline value of the lung resist-ance (RL) and dynamic compliance of respiratory system (Cdyn), DMSO (0.3 ml/kg) and FK224 (1mg/kg) wereadministered by injection through jugular vein respectively. A rodent respirator with dry 5% CO2-95% O2 mixture atroom temperature provided mechanical ventilation ( VT 8ml/animal, 100breaths/min) for 5min. RL and Cdyn of 2groups were measured after isocapnic hyperpnea challenge. Results In DMSO control group, isocapnic hyper-pnea of dry gas elicited a marked increase in RL and decrease in Cdyn. RL and Cdyn of FK224 group did not changesignificantly. Conclusion FK224 can inhibit the increase in RL and decrease in Cdyn caused by isocapnic hy-perpnea in guinea pigs. And antagonists of tachykinins receptors might have effect on prophylaxis and treatment inexercise-induced asthma.

Substance P and its tachykinin NK1 receptor: a novel neuroprotective target for Parkinson's disease

Parkinson＇s disease （PD） is the most common motor neurode- generative disorder affecting approximately 4 million people worldwide. Although PD presents primarily with motor dysfunction, non-motor symptoms including cognitive decline, mood disorders, reduced olfaction and constipation are also of- ten present, with some of these non-motor symptoms even pre- senting prior to the onset of motor symptoms. It is well known that PD is largely caused by the gradual degeneration of dopa- minergic neurons within the substantia nigra pars compacta （SNc）, along with the presence of protein aggregates called Lewy bodies, which consist primarily of ct-synuclein and are found in the cytoplasm of surviving neurons. This ongoing cell loss and Lewy body pathology is not confined to the SNc, but is also seen in other brain regions implicated in PD pathogenesis such as the locus ceruleus.

炎症性递质(白三烯、TXA_2、tachykinin等)与支气管哮喘

支气管哮喘做为呼吸系统的重要疾病之一 ,一直为医学界所关注。不仅WHO制订了全球哮喘诊治创议 ,各国亦制订了各自的诊治指南以防治致死性哮喘。研究不仅关注成人哮喘 ,而且愈益注意儿童哮喘。不仅进行大规模的流行病学调查 ,而且从基础研究到临床诊治 ,近年来都有较大进展。本专辑选译自《日本临床》杂志 2 0 0 1年第 59卷第 1 0期特集—气管支喘息———基础·临床の进步と展望。相信本专辑会给呼吸科医生提供一系列基础、临床研究信息。

Expression of Preprotachykinin-I (PPT-I), Neurokinin-1 (NK-1) and Neurokinin-2 (NK-2) in Breast Cancer Cells Improves Tumor Cell Survival in Bone Marrow in the Early Stage of Metastasis

OBJECTIVE To study the potential relationship between the expression of PPT-I, NK-1, NK2 and the development of breast cancer cells in bone marrow stroma and to provide evidence of potential molecular mechanisms of breast cancer patients. of bone metastasis in early stage METHODS The cocultures of breast cancer cell line T-47D and marrow-derived mesenchymal stem cells （MSC） were established with equal numbers. T-47D cells were separated from the coculture system at 48 h and 96 h after coculture by MACS magnetic cell sorting （MicroBeads）. The expression of PPT-I, NK-1, NK-2 in T-47D was then examined before and after coculture by real-time PCR and by Western blot. Alterations in cellular ultrastructure of T-47D cells were detected before and after coculture under electron microscope. Finally, changes in cell cycle distribution were examined by flow cytometry, and growth curves from before and after coculture were drawn and analyzed. RESULTS Following coculture of T-47D and MSC, the expression of PPT-I mRNA and protein was significantly upregulated, while the expression of NK-1 and NK-2 mRNA and protein was greatly downregulated. The analysis of cell cycle distribution by flow cytometry showed that the proportion of T-47D during S phase was increased, and the duration of the G2/M phase was sharply decreased. Under electron microscope, we observed that the synthesis of hereditary material was increased, but the hepatin granules were shown prominent stacking in T-47D cells. These results suggest that although the synthesis of DNA was increased, the proliferation of cells was inhibited after coculture. The cell growth curve confirmed the findings from the observation under the electron microscope and flow cytometry. CONCLUSION Tumor cells could survive through the upregulation in expression of preprotachykinin-I gene during early bone metastasis in breast cancer. The phenomenon of growth suppression in breast cancer cells after coculture in the current study could be induced by downregulation in expression of NK-1 and NK-2.

速激肽P物质在急性心肌梗死中的作用

P物质（substance P，SP）是发现最早的速激肽之一，是速激肽（tachykinin，TK）家族的重要成员。1931年由VonEuler和Gaddum在马大脑和肠中提取乙酰胆碱时意外发现，并命名为P物质。SP广泛分布神经系统和心血管系统，如心内神经节、冠状动脉、心房、心室及传导系统等，具有多种生物学效应。

Expression of tachykinin receptors in Xenopus oocytes injected with poly(A)^+RNA from cat dorsal root ganglion

The expression of the types of tachykinin receptors in the dorsal root ganglion (DRG) neurons by means of Xenopus oocyte expressing system was studied. Poly(A) +RNAs were extracted from cat cervical and lumbar DRG. Two days after injection of Poly(A) +RNAs, the oocytes were recorded with the two electrode voltage clamp technique. In the oocytes injected with DRG poly(A) +RNA,[Sar 9,Met(O 2) 11 ] substance P(Sar SP, 1 μmol/L), neurokinin A (NKA,1 μmol/L) or [β Ala 8] neurokinin A (4-10) (Ala NKA, 1 μmol/L) produced an inward current comprising a rapid spike and a long sustained oscillatory component for several minutes. Sar SP induced response was blocked by NK 1 antagonist L 668, 169 (1 μmol/L), but not by NK 2 antagonist L 659,877(1μmol/L). In contrast, Ala NKA and NKA responses were only blocked by L 659,877. The oocytes injected with DH Poly(A) +RNA also responded to Sar SP and NKA with similar inward currents, which were selectively blocked by L 668,169 and L 659,877, respectively. These tachykinins induced responses had a potent desensitization. The present data indicate expression of NK 1 and NK 2 receptors in DRG neurons, suggesting that there may be tachykinin autoreceptors on the nociceptive primary afferent terminals.

SYNTHESIS AND BIOLOGICAL ACTIVITY OF A NEW FROG SKIN PEPTIDE, RANAMARGARIN

A new frog skin peptide, ranamargarin depicted as H-Asp-Asp-Ala-Ser-Asp-Arg-Ala-Lys-Lys-Phe-Tyr-Gly-Leu-Met-NH_(2′), was synthesized by the conventionalmethod. Comparisons of chemical and biological properties of both the synthetic and natural ranamargarins indicated that they were identical, so the chemical structure of ranamargarin was confirmed. Preliminary pharmacological study showed that ranamargarin was highly selective towards the SP-P subtype receptor.