Cross-regulation between colocalized nicotinic acetylcholine and 5-HT3 serotonin receptors on presynaptic nerve terminals  

作　　者：Robert A NICHOLS JohnJ D OUGHERTY 

机构地区：[1]Department of Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, PA 19102, USA [2]Department of Cell and Molecular Biology, University of Hawai'i at Manoa, Honolulu, HI, 96813, USA

出　　处：《Acta Pharmacologica Sinica》2009年第6期788-794,共7页中国药理学报（英文版）

摘　　要：Aim： Substantial colocalization of functionally independent a4 nicotinic acetylcholine receptors and 5-HT3 serotonin receptors on presynaptic terminals has been observed in brain. The present study was aimed at addressing whether nicotinic acetylcholine receptors and 5-HT3 serotonin receptors interact on the same presynaptic terminal, suggesting a convergence of cholinergic and serotonergic regulation. Methods： Ca^2＋ responses in individual, isolated nerve endings purified from rat striatum were measured using confocal imaging. Results： Application of 500 nmol/L nicotine following sustained stimulation with the highly selective 5-HT3 receptor agonist m-chlorophenylbiguanide at 100 nmol/L resulted in markedly reduced Ca^2＋ responses （28% of control） in only those striatal nerve endings that originally responded to m-chlorophenylbiguanide. The cross-regulation developed over several minutes. Presynaptic nerve endings that had not responded to m-chlorophenylbiguanide, indicating that 5-HT3 receptors were not present, displayed typical responses to nicotine. Application of m-chlorophenylbiguanide folIowing sustained stimulation with nicotine resulted in partially attenuated Ca^2＋ responses （49% of control）. Application of m-chlorophenylbiguanide following sustained stimulation with m-chlorophenylbiguanide also resulted in a strong attenuation of Ca^2＋ responses （12% of control）, whereas nicotine-induced Ca^2＋ responses following sustained stimulation with nicotine were not significantly different from control. Conclusion： These results indicate that the presynaptic Ca^2＋ increases evoked by either 5-HT3 receptor or nicotinic acetylcholine receptor activation regulate subsequent responses to 5-HT3 receptor activation, but that only 5-HT3 receptors cross-regulate subsequent nicotinic acetylcholine receptor-mediated responses. The findings suggest a specific interaction between the two receptor systems in the same striatal nerve terminal, likely involving Ca^2＋-dependent intracellular pAim： Substantial colocalization of functionally independent a4 nicotinic acetylcholine receptors and 5-HT3 serotonin receptors on presynaptic terminals has been observed in brain. The present study was aimed at addressing whether nicotinic acetylcholine receptors and 5-HT3 serotonin receptors interact on the same presynaptic terminal, suggesting a convergence of cholinergic and serotonergic regulation. Methods： Ca^2＋ responses in individual, isolated nerve endings purified from rat striatum were measured using confocal imaging. Results： Application of 500 nmol/L nicotine following sustained stimulation with the highly selective 5-HT3 receptor agonist m-chlorophenylbiguanide at 100 nmol/L resulted in markedly reduced Ca^2＋ responses （28% of control） in only those striatal nerve endings that originally responded to m-chlorophenylbiguanide. The cross-regulation developed over several minutes. Presynaptic nerve endings that had not responded to m-chlorophenylbiguanide, indicating that 5-HT3 receptors were not present, displayed typical responses to nicotine. Application of m-chlorophenylbiguanide folIowing sustained stimulation with nicotine resulted in partially attenuated Ca^2＋ responses （49% of control）. Application of m-chlorophenylbiguanide following sustained stimulation with m-chlorophenylbiguanide also resulted in a strong attenuation of Ca^2＋ responses （12% of control）, whereas nicotine-induced Ca^2＋ responses following sustained stimulation with nicotine were not significantly different from control. Conclusion： These results indicate that the presynaptic Ca^2＋ increases evoked by either 5-HT3 receptor or nicotinic acetylcholine receptor activation regulate subsequent responses to 5-HT3 receptor activation, but that only 5-HT3 receptors cross-regulate subsequent nicotinic acetylcholine receptor-mediated responses. The findings suggest a specific interaction between the two receptor systems in the same striatal nerve terminal, likely involving Ca^2＋-dependent intracellular p

关 键 词：presynaptic calcium regulation nicotinic receptors serotonin receptors 

分 类 号：R962[医药卫生—药理学] R161[医药卫生—药学]