@article{APS5222,
author = {John J Dougherty and Robert A Nichols},
title = {Cross-regulation between colocalized nicotinic acetylcholine and 5-HT 3 serotonin receptors on presynaptic nerve terminals},
journal = {Acta Pharmacologica Sinica},
volume = {30},
number = {6},
year = {2016},
keywords = {},
abstract = {Aim: Substantial colocalization of functionally independent α4 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: Ca2+ 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 Ca2+ 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 following sustained stimulation with nicotine resulted in partially attenuated Ca2+ responses (49% of control). Application of m-chlorophenylbiguanide following sustained stimulation with m-chlorophenylbiguanide also resulted in a strong attenuation of Ca2+ responses (12% of control), whereas nicotine-induced Ca2+ responses following sustained stimulation with nicotine were not significantly different from control.
Conclusion: These results indicate that the presynaptic Ca2+ 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 Ca2+-dependent intracellular pathways that regulate these signaling systems at one or more levels.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/5222}
}