Purpose: To characterize prejunctional 5-HT heteroreceptors which modulate nacetylcholine (3 H-ACh release) in isolated rabbit and human iris-ciliary bodies (ICBS) . Methods: ICB tissue segments were incubated with H-...Purpose: To characterize prejunctional 5-HT heteroreceptors which modulate nacetylcholine (3 H-ACh release) in isolated rabbit and human iris-ciliary bodies (ICBS) . Methods: ICB tissue segments were incubated with H-choline, superfused and electrically stimulated four times (S1,S2,S3,S4) at 3 - 10 Hz for 1 min to elicit 3H-ACh. secretion. Test agents (5-HT agonists and antagonists) were added before S2,S3 and S4 and their effects determined by the stimulation ratio (Sx/S1) of evoked 3H-ACh. release. 3H-ACh in super-fusate fractions was fractionated and quantified by ion exchange chromatography. Results: In rabbit ICBs, evoked 3H-ACh. release was enhanced in a concentration-dependent manner by 5-HT (10- 9 - 10-5 M, EC50 = 5.8× 10-8 M). The maximum effect of 5-HT (10-6M) corresponded to a 45. 14 ± 7.40%) (n = 6) increase in 3H-ACh release. Higher concentrations of 5-HT ( > 10- M) induced desensitization. The response to 5-HT ( 10-6 M) in the presence of the 5-HT3/4 antagonist tropisetron (10-9 M) ,展开更多
Objective To observe the influence of Kaixin Powder on ethology,content of 5-HT in the hippocampus, expression of m RNA, and protein in 5-HT1 A and 5-HT2 A receptors in the hippocampus of depressed rats induced by chr...Objective To observe the influence of Kaixin Powder on ethology,content of 5-HT in the hippocampus, expression of m RNA, and protein in 5-HT1 A and 5-HT2 A receptors in the hippocampus of depressed rats induced by chronic unpredictable mild stress（CUMS）. Methods Twenty-four male Wistar rats were randomly divided into blank,model, Trazodone, and Kaixin Powder groups, six rats in each group. In addition to the blank control group, other groups were established the depression model induced by CUMS combined with isolated feeding. At the same time, Trazodone group and Kaixin Powder group were treated with corresponding drugs for 3 weeks. After 3 weeks of administration, the rats were sacrificed, and a series of indexes were measured such as the contents of 5-HT, m RNA expression levels of 5-HT1 A and 5-HT2 A receptors, protein expression levels of 5-HT1 A and 5-HT2 A receptors, and so on. Results A series of indexes in the model group were decreased significantly such as the body weight growth, the sugar water intake, the score of Open Field Test, the content of5-HT in the hippocampus, expression of m RNA, and protein in 5-HT1 A receptor, while the expression of m RNA and protein in 5-HT2 A receptor were increased significantly.Compared with the model group, the indexes were ameliorated in Trazodone and Kaixin Powder groups. Kaixin Powder is better than Trazodone in decreasing the level of protein in 5-HT2 A receptor. Conclusion The result indicated that the depression performance of depressed rats induced by CUMS can be ameliorated by Kaixin Powder,and the mechanism maybe concerned with increasing the contents of 5-HT, exciting 5-HT1 A receptor, and antagonising 5- HT2 A receptor.展开更多
Objective To outline the recent progress in drug discovery for medication-induced dyskinesia(Parkinson disease,PD)and tardive diskinesia(schizophrenia)with emphasizing the role of 5-HT1A receptor.Methods Development o...Objective To outline the recent progress in drug discovery for medication-induced dyskinesia(Parkinson disease,PD)and tardive diskinesia(schizophrenia)with emphasizing the role of 5-HT1A receptor.Methods Development of extrapyramidal syndrome(EPS)followed either chronic L-DOPA administration in PD(L-DOPA-induced dyskinesia,LID)or antipsychotic treatment in schizophrenia(Tardive dyskinesia,TD)remains a challenge in the clinical practice and drug discovery.In addition to the abnormal dopamine activity in the nigrostrial area that contributes to the LID or TD,recent information indicates that 5-HT1A receptor also plays an important role which is merging as promising target in treatment of LID or TD.Results l-Stepholidine(l-SPD),isolated from the Chinese herb Stephania,is known as a dual dopamine receptor agent(D1 receptor agonistic and D2 antagonistic activity).In addition,we further demonstrated that l-SPD binds to 5-HT1A receptor and exhibits a partial agonistic activity.In LID rat model,l-SPD not only attenuated the development of L-DOPA-induced dyskinesia(LID),but also relived the established LID.The effect of l-SPD on LID was completely blocked by pretreatment of 5-HT1A receptor antagonist,indicating the role of 5-HT1A receptor.Furthermore,we designed and synthesis a dual dopamine/5-HT1A receptor agonist MCL-135,which also exhibits a significant relief on LID while elicits its antiparkinsonian action.Conclusions 5-HT1A receptor plys an important role in the development of LID,targeted to dual dopamine/5-HT receptor may represent a promising strategy for drug design and discovery in LID and TD treatment.展开更多
Hepatocytes were isolated from livers of adult male SpragueDawley rats and cultured in Williams'E Medium with 3 H thymidine. The effect of 5hydroxytryptamine (5HT) was investigated through adding various concentra...Hepatocytes were isolated from livers of adult male SpragueDawley rats and cultured in Williams'E Medium with 3 H thymidine. The effect of 5hydroxytryptamine (5HT) was investigated through adding various concentrations (10-810-3 mol/L) of 5HT to the hepatocyte cultures in the presence or absence of epidermal growth factor (EGF) and insulin. The involvement of 5HT2 receptor was examined by adding a 5HT2 receptor antagonist, ketanserin (10-6 mol/L), to some of the cultures containing 5HT. The increment of DNA synthesis was measured by 3 H thymidine incorporation. The results showed that 5HT2 (10-6 mol/L) significantly (P<005) increased the amount of DNA synthesis induced by EGF and insulin in the cultured adult rat hepaptocytes. The effect of 5HT in enhancing DNA synthesis began to appear at a concentration between 10-7 and 10-6 mol/L and reached maximum at concentrations of 10-4 mol/L. The enhancement of DNA synthesis by 5HT was significantly (P<005) antagonized by ketanserin, suggesting that this effect of 5HT was mediated by 5HT2 receptor subtype.展开更多
The localizations of 5-hydroxytryptamine receptor (5-HTR) at light and electron microscopic levels and its quantitative analysis in human placentas were studied by using immunohistochemistry and in situ hybridization....The localizations of 5-hydroxytryptamine receptor (5-HTR) at light and electron microscopic levels and its quantitative analysis in human placentas were studied by using immunohistochemistry and in situ hybridization. Both syncytiotrophoblast and cytotrophoblast in placental villi and fetal white blood cells in villose capillary cavity showed 5-HT receptor immunoreactivity, with 5-HT 1A receptor mRNA hybridized signal detected in cytoplasm. But the stromal cells and capillary endothelium in placental villi showed 5-HT receptor immunoreactivity in cytoplasm, without 5_HT\-1A receptor mRNA hybridized signal detected. This suggested that two layers of trophoblast cells may produce 5-HT 1 and 5-HT 2 receptors, that the stromal cells and capillary endothelium in placental villi may only produce 5-HT 2 receptor. By immunohistochemistry at electron microscopic level, the small flattened vesicles and large dense cored vesicle within trophoblast cells showed 5-HT receptor immunoreactivity. This suggested that it may be the result of 5-HT receptors internalization and transportion. Using a quantitative immunohistochemical method, the contents of 5-HT receptor in placenta were higher during the 6th week of gestation, and decreased in 7th and 8th, reoccurred the second peak in the 9th, reduced gradually during the 10th, 20th and 40th of the gestation period. These changes paralleled the contents of 5-HT in the authors’ studies, reflecting that 5-HT may be one of the most important bioactive substances in placental self-regulation.展开更多
Objective:To explore the 5-HT mechanism of stress . Methods:The method of polymerase chain reaction (PCR) was used to detect the presence of 5-HT receptor subtypes in the hippocampus,hypothalamic and midbrain of the r...Objective:To explore the 5-HT mechanism of stress . Methods:The method of polymerase chain reaction (PCR) was used to detect the presence of 5-HT receptor subtypes in the hippocampus,hypothalamic and midbrain of the rat after 30days of movement restrict compared with normal cage control groups (CC) . The specific oligonucleotide primers were synthesized based on the complementary DNA sequence for each of the rat 5-HT 1A and 5-HT 2A receptor subtypes . Results : The expression of 5-HT 1A receptor subtypes in each regions of the rat brain after movement restrict were signifcantly lower than that of the CC groups, and the expression of 5-HT 2A receptor subtype were signifcantly higher( P <0.01-0.05).Conclusions : 5-HT 1A and 5-HT 2A receptors may be invovled in the stress of the rat and may have opposite effects with respect to certain functions.展开更多
基金This study was supported by NIH grant EYO5246,the Kentucky Lions Eye Foundation and an unrestricted grant from Research to Prevent Blindness.Inc
文摘Purpose: To characterize prejunctional 5-HT heteroreceptors which modulate nacetylcholine (3 H-ACh release) in isolated rabbit and human iris-ciliary bodies (ICBS) . Methods: ICB tissue segments were incubated with H-choline, superfused and electrically stimulated four times (S1,S2,S3,S4) at 3 - 10 Hz for 1 min to elicit 3H-ACh. secretion. Test agents (5-HT agonists and antagonists) were added before S2,S3 and S4 and their effects determined by the stimulation ratio (Sx/S1) of evoked 3H-ACh. release. 3H-ACh in super-fusate fractions was fractionated and quantified by ion exchange chromatography. Results: In rabbit ICBs, evoked 3H-ACh. release was enhanced in a concentration-dependent manner by 5-HT (10- 9 - 10-5 M, EC50 = 5.8× 10-8 M). The maximum effect of 5-HT (10-6M) corresponded to a 45. 14 ± 7.40%) (n = 6) increase in 3H-ACh release. Higher concentrations of 5-HT ( > 10- M) induced desensitization. The response to 5-HT ( 10-6 M) in the presence of the 5-HT3/4 antagonist tropisetron (10-9 M) ,
基金National Natural Science Fund of China(NO.81072744)
文摘Objective To observe the influence of Kaixin Powder on ethology,content of 5-HT in the hippocampus, expression of m RNA, and protein in 5-HT1 A and 5-HT2 A receptors in the hippocampus of depressed rats induced by chronic unpredictable mild stress（CUMS）. Methods Twenty-four male Wistar rats were randomly divided into blank,model, Trazodone, and Kaixin Powder groups, six rats in each group. In addition to the blank control group, other groups were established the depression model induced by CUMS combined with isolated feeding. At the same time, Trazodone group and Kaixin Powder group were treated with corresponding drugs for 3 weeks. After 3 weeks of administration, the rats were sacrificed, and a series of indexes were measured such as the contents of 5-HT, m RNA expression levels of 5-HT1 A and 5-HT2 A receptors, protein expression levels of 5-HT1 A and 5-HT2 A receptors, and so on. Results A series of indexes in the model group were decreased significantly such as the body weight growth, the sugar water intake, the score of Open Field Test, the content of5-HT in the hippocampus, expression of m RNA, and protein in 5-HT1 A receptor, while the expression of m RNA and protein in 5-HT2 A receptor were increased significantly.Compared with the model group, the indexes were ameliorated in Trazodone and Kaixin Powder groups. Kaixin Powder is better than Trazodone in decreasing the level of protein in 5-HT2 A receptor. Conclusion The result indicated that the depression performance of depressed rats induced by CUMS can be ameliorated by Kaixin Powder,and the mechanism maybe concerned with increasing the contents of 5-HT, exciting 5-HT1 A receptor, and antagonising 5- HT2 A receptor.
文摘Objective To outline the recent progress in drug discovery for medication-induced dyskinesia(Parkinson disease,PD)and tardive diskinesia(schizophrenia)with emphasizing the role of 5-HT1A receptor.Methods Development of extrapyramidal syndrome(EPS)followed either chronic L-DOPA administration in PD(L-DOPA-induced dyskinesia,LID)or antipsychotic treatment in schizophrenia(Tardive dyskinesia,TD)remains a challenge in the clinical practice and drug discovery.In addition to the abnormal dopamine activity in the nigrostrial area that contributes to the LID or TD,recent information indicates that 5-HT1A receptor also plays an important role which is merging as promising target in treatment of LID or TD.Results l-Stepholidine(l-SPD),isolated from the Chinese herb Stephania,is known as a dual dopamine receptor agent(D1 receptor agonistic and D2 antagonistic activity).In addition,we further demonstrated that l-SPD binds to 5-HT1A receptor and exhibits a partial agonistic activity.In LID rat model,l-SPD not only attenuated the development of L-DOPA-induced dyskinesia(LID),but also relived the established LID.The effect of l-SPD on LID was completely blocked by pretreatment of 5-HT1A receptor antagonist,indicating the role of 5-HT1A receptor.Furthermore,we designed and synthesis a dual dopamine/5-HT1A receptor agonist MCL-135,which also exhibits a significant relief on LID while elicits its antiparkinsonian action.Conclusions 5-HT1A receptor plys an important role in the development of LID,targeted to dual dopamine/5-HT receptor may represent a promising strategy for drug design and discovery in LID and TD treatment.
文摘Hepatocytes were isolated from livers of adult male SpragueDawley rats and cultured in Williams'E Medium with 3 H thymidine. The effect of 5hydroxytryptamine (5HT) was investigated through adding various concentrations (10-810-3 mol/L) of 5HT to the hepatocyte cultures in the presence or absence of epidermal growth factor (EGF) and insulin. The involvement of 5HT2 receptor was examined by adding a 5HT2 receptor antagonist, ketanserin (10-6 mol/L), to some of the cultures containing 5HT. The increment of DNA synthesis was measured by 3 H thymidine incorporation. The results showed that 5HT2 (10-6 mol/L) significantly (P<005) increased the amount of DNA synthesis induced by EGF and insulin in the cultured adult rat hepaptocytes. The effect of 5HT in enhancing DNA synthesis began to appear at a concentration between 10-7 and 10-6 mol/L and reached maximum at concentrations of 10-4 mol/L. The enhancement of DNA synthesis by 5HT was significantly (P<005) antagonized by ketanserin, suggesting that this effect of 5HT was mediated by 5HT2 receptor subtype.
文摘The localizations of 5-hydroxytryptamine receptor (5-HTR) at light and electron microscopic levels and its quantitative analysis in human placentas were studied by using immunohistochemistry and in situ hybridization. Both syncytiotrophoblast and cytotrophoblast in placental villi and fetal white blood cells in villose capillary cavity showed 5-HT receptor immunoreactivity, with 5-HT 1A receptor mRNA hybridized signal detected in cytoplasm. But the stromal cells and capillary endothelium in placental villi showed 5-HT receptor immunoreactivity in cytoplasm, without 5_HT\-1A receptor mRNA hybridized signal detected. This suggested that two layers of trophoblast cells may produce 5-HT 1 and 5-HT 2 receptors, that the stromal cells and capillary endothelium in placental villi may only produce 5-HT 2 receptor. By immunohistochemistry at electron microscopic level, the small flattened vesicles and large dense cored vesicle within trophoblast cells showed 5-HT receptor immunoreactivity. This suggested that it may be the result of 5-HT receptors internalization and transportion. Using a quantitative immunohistochemical method, the contents of 5-HT receptor in placenta were higher during the 6th week of gestation, and decreased in 7th and 8th, reoccurred the second peak in the 9th, reduced gradually during the 10th, 20th and 40th of the gestation period. These changes paralleled the contents of 5-HT in the authors’ studies, reflecting that 5-HT may be one of the most important bioactive substances in placental self-regulation.
文摘Objective:To explore the 5-HT mechanism of stress . Methods:The method of polymerase chain reaction (PCR) was used to detect the presence of 5-HT receptor subtypes in the hippocampus,hypothalamic and midbrain of the rat after 30days of movement restrict compared with normal cage control groups (CC) . The specific oligonucleotide primers were synthesized based on the complementary DNA sequence for each of the rat 5-HT 1A and 5-HT 2A receptor subtypes . Results : The expression of 5-HT 1A receptor subtypes in each regions of the rat brain after movement restrict were signifcantly lower than that of the CC groups, and the expression of 5-HT 2A receptor subtype were signifcantly higher( P <0.01-0.05).Conclusions : 5-HT 1A and 5-HT 2A receptors may be invovled in the stress of the rat and may have opposite effects with respect to certain functions.
