Substance P protects against desensitization of the nicotinic response in isolated adrenal chromaffin cells.
Substance P, a peptide endogenous to the splanchnic nerve, is known to inhibit the acetylcholine-and 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(-5) M) completely protected against desensitization of catecholamine release produced by acetylcholine at 37 degrees C or 23 degrees C and by nicotine at 23 degrees C; substance P also afforded appreciable protection against nicotine-induced desensitization at 37 degrees 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.
D000109:Acetylcholine / Q000494:pharmacology*; D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002837:Chromaffin Granules / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007700:Kinetics; D009538:Nicotine / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology*; D014403:Tubocurarine / Q000494:pharmacology
D013373:Substance P; D009538:Nicotine; D000109:Acetylcholine; D011188:Potassium; D014403:Tubocurarine; D009638:Norepinephrine