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

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 c oncentration 10(-7)/10(-6) M markedly raised it, and the effect was an nulled by equimolar concentrations of SP. Both SP and SPA (10(-6) M) i ncreased 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-dependently (from 10(-8) M t o 10(-6) M) partially inhibited maximally ACTH (10(-8) M)-induced stim ulation of B secretion of dispersed cells, and unexpectedly a similar effect was observed after SPA exposure. In light of these findings, th e 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 ro le in quenching, via a receptor-independent mechanism, the exceedingly high glucocorticoid responses to ACTH of rat adrenocortical cells.