Substance P inhibits catecholamine biosynthesis stimulated by carbamylcholine in cultured adrenal chromaffin cells.

The effect of substance P on catecholamine biosynthesis was examined using cultured bovine adrenal chromaffin cells as a model for the sympathoadrenergic system. Substance P markedly inhibited the formation of [14C]catecholamines from L-[14C]tyrosine stimulated by cholinergic agonist, but caused no significant effect on the biosynthesis stimulated by depolarizing agent. In addition, this inhibitory action was completely prevented by the addition of substance P antagonists. Under the conditions in which the inhibition of catecholamine biosynthesis was observed, substance P also inhibited the influx of extracellular 45Ca2+ into these cells, and this inhibitory action on Ca2+ influx was almost identical to that on the biosynthesis. These results provide evidence for a possible role of substance P as a putative neuromodulator in the sympathoadrenergic system.