Cellular mechanism of substance P in the regulation of corticosteroid secretion by newt adrenal gland

In this work, we have studied the effects and the possible cellular mechanism of Substance P (SP) on corticosteroid secretion by the adrenal gland of the urodele crested newt, Triturus carnifex. Adrenals were in 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 cyclase (sGC). PGE(2), corticosterone, and aldosterone release and NOS activity were determined. SP, PGE(2), NO donor, and cGMP analogue increased corticosterone and aldosterone; SP and PGE(2) increased NOS, and SP increased PGE(2). PLA2, AC, COX, NOS, and sGC inhibitors counteracted SP and PGE(2) effects, except for PLA2, which did not affect PGE(2). These results suggest that SP exhibits a stimulatory role on the corticosteroidogenesis of T. carnifex adrenal gland. In particular SP enhances PLA2 activity, increasing PGE(2); this prostaglandin affects AC, which, in turn, enhances NO, and the latter therefore affects sGC, with the consequent corticosteroidogenesis increase. (C) 1997 Academic Press.