SEROTONIN MODULATES NICOTINIC RESPONSES OF ADRENAL CHROMAFFIN CELLS

5-Hydroxytryptamine (5-HT) specifically and reversibly inhibits nicoti ne-induced currents and catecholamine release in bovine adrenal chroma ffin cells in culture. Pharmacological analysis indicates that the inh ibition is not mediated by known 5-HT receptor subtypes. The inhibitio n is noncompetitive over a range of nicotine concentrations between 1 and 1 00 muM. Preincubation with either 5-HT or substance P significan tly protects the response from nicotine-induced desensitization. It is concluded that 5-HT inhibits nicotinic acetylcholine receptors on bov ine adrenal chromaffin cells, probably by binding to a noncompetitive site on the receptor itself. Because both blood and the chromaffin cel ls contain 5-HT, the inhibition provides an opportunity for negative c ontrol of catecholamine secretion from the adrenals.