Effects of substance P and its antagonist spantide on corticosterone secretion and cytosolic free calcium concentration of dispersed zona fasciculata-reticularis cells of the rat adrenal cortex

Abstract

Substance P (SP) did not change basal corticosterone (B) secretion of dispersed zona fasciculata-reticularis cells of the rat adrenal cortex. Conversely, spantide II (SPA), an antagonist of SP receptors, at a concentration 10⁻⁷/10⁻⁶ M markedly raised it, and the effect was annulled by equimolar concentrations of SP. Both SP and SPA (10⁻⁶ M) increased cytosolic free calcium concentration in our cell preparations; however, the response to SP was immediate, while that to SPA showed a lag-period of 4–5 min. SP concentration-dependency (from 10⁻⁸ M to 10⁻⁶ M) partially inhibited maximally ACTH (10⁻⁸ M)-induced stimulation of B secretion of dispersed cells, and unexpectedly a similar effect was observed after SPA exposure. In light of these findings, the conclusion is drawn that SP, under basal conditions, does not exert a direct modulatory action of B secretion of rat adrenocortical cells. However, the possibility remains to be explored that SP may play a role in quenching, via a receptor-independent mechanism, the exceedingly high glucocorticoid responses to ACTH of rat adrenocortical cells.