| 19498419 |
Dougherty JJ, Nichols RA: Cross-regulation between colocalized nicotinic acetylcholine and 5-HT3 serotonin receptors on presynaptic nerve terminals. J Neurosci. 2008 Nov 19;28(47):12465-76.
AIM: Substantial colocalization of functionally independent alpha4 nicotinic acetylcholine receptors and 5-HT (3) serotonin receptors on presynaptic terminals has been observed in brain. The present study was aimed at addressing whether nicotinic acetylcholine receptors and 5-HT (3) 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-HT (3) 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-HT (3) receptors were not present, displayed typical responses to nicotine. Application of m-chlorophenylbiguanide following 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-HT (3) receptor or nicotinic acetylcholine receptor activation regulate subsequent responses to 5-HT (3) receptor activation, but that only 5-HT (3) 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 pathways that regulate these signaling systems at one or more levels. |
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