CELLULAR MECHANISM OF SUBSTANCE-P IN THE REGULATION OF CORTICOSTEROIDSECRETION BY NEWT ADRENAL-GLAND

In this work, we have studied the effects and the possible cellular me chanism of Substance P (SP) on corticosteroid secretion by the adrenal gland of the urodele crested newt, Triturus carnifex. Adrenals were i n vitro superfused with SP, prostaglandin E-2 (PGE(2)), nitric oxide ( NO) donor, cyclic GMP (cGMP) analogue, and inhibitors of phospholipase A1, phospholipase A2 (PLA2), phospholipase C, adenylate cyclase (AC), cyclooxygenase (COX), NO synthase (NOS), and soluble guanylate cyclas e (sGC). PGE(2), corticosterone, and aldosterone release and NOS activ ity were determined. SP, PGE(2), NO donor, and cGMP analogue increased corticosterone and aldosterone; SP and PGE(2) increased NOS, and SP i ncreased PGE(2). PLA2, AC, COX, NOS, and sGC inhibitors counteracted S P and PGE(2) effects, except for PLA2, which did not affect PGE(2). Th ese results suggest that SP exhibits a stimulatory role on the cortico steroidogenesis of T. carnifex adrenal gland. In particular SP enhance s PLA2 activity, increasing PGE(2); this prostaglandin affects AC, whi ch, in turn, enhances NO, and the latter therefore affects sGC, with t he consequent corticosteroidogenesis increase. (C) 1997 Academic Press .