Serotonin-mediated modulation of acetylcholine-induced intracellular calcium responses in chromaffin cells isolated from the rat adrenal medulla

We examined serotonin (5-HT)-mediated modulation of acetylcholine (ACh)-induced intracellular Ca2+ ([Ca2+]i) responses in rat adrenal chromaffin cells using calcium imaging. 5-HT did not induce any [Ca2+]i response in clustered chromaffin cells. However, the magnitude of ACh-induced [Ca2+]i increases in the same specimens was inhibited in the presence of 5-HT. ACh-induced [Ca2+]i increases in chromaffin cells were also inhibited by the 5-HT1A receptor agonist, 8-hydroxy-2-(dipropylamino) tetralin hydrobromide, but were not changed by the 5-HT1B, 5-HT2, or 5-HT3 receptor agonists, CP93129, α-methyl-5-HT, or 1-(m-chlorophenyl) biguanide, respectively. RT-PCR analysis detected the expression of all 5-HT receptor subtype mRNAs, except for 5-HT5 receptors, in extracts of the adrenal medulla. Immunohistochemistry revealed that immunoreactivity for 5-HT1A receptor was located in the chromaffin cells immunoreactive for the biosynthetic enzyme for noradrenaline, dopamine β-hydroxylase. These results suggest that 5-HT inhibits ACh-induced excitability in adrenal chromaffin cells via the 5-HT1A receptor in order to reduce catecholamine release during preganglionic sympathetic stimuli.