Substance P Protects Against Desensitization of the Nicotinic Response in Isolated Adrenal Chromaffin Cells

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Abstract
Substance P, a peptide endogenous to the splanchnic nerve, is known to inhibit the acetylcholineand nicotine‐induced release of catecholamines from isolated adrenal chromaffin cells. In the present study the effect of substance P on desensitization of catecholamine release from these cells was examined. Substance P (10−5M) completely protected against desensitization of catecholamine release produced by acetylcholine at 37°C or 23°C and by nicotine at 23°C; substance P also afforded appreciable protection against nicotine‐induced desensitization at 37°C. The peptide had no effect on K+‐induced desensitization of catecholamine release. Like substance P, d‐tubocurarine also prevented nicotinic desensitization. Substance P prevented both of two components of nicotinic desensitization, i.e. the Ca2+‐dependent component and the Ca2+‐independent, depletion‐independent component of desensitization. Substance P had little effect on subsequent catecholamine uptake, indicating that substance P's protection against desensitization is a result of facilitation of catecholamine release rather than inhibition of catecholamine reuptake. Nicotine‐induced catecholamine release and nicotinic desensitization of catecholamine release were Na+‐independent, although substance P's inhibition of nicotine‐induced catecholamine release was reduced by extracellular Na+. These in vitro studies suggest a similar role for substance P in vivo: substance P's protection against nicotinic desensitization may ensure a maintained output of adrenal catecholamines during stress, when the splanchnic nerve releases large amounts of acetylcholine.