RANAKININ, A NATURALLY-OCCURRING TACHYKININ, STIMULATES PHOSPHOLIPASE-C ACTIVITY IN THE FROG ADRENAL-GLAND

We have previously shown that the frog adrenal gland is innervated by a dense network of fibers containing ranakinin, one of the endogenous tachykinins in the amphibian Rana ridibunda, and we have found that ra nakinin stimulates in vitro corticosteroid secretion by frog adrenal t issue. To elucidate the mechanism of action of ranakinin on the frog a drenal gland, we investigated the effect of ranakinin on cAMP formatio n and polyphosphoinositide metabolism. Incubation of frog adrenal expl ants with various tachykinins, including ranakinin, substance P, neuro kinin A, or neurokinin B, did not produce any significant modification of cAMP concentrations. In contrast, ranakinin induced a time-and dos e-dependent stimulation of inositol phosphate formation with a concomi tant decrease in membrane polyphosphoinositides. Pretreatment of the t issue slices with the phospholipase C inhibitor U-73122 or with pertus sis toxin completely abolished the stimulatory effect of ranakinin on inositol phosphate formation. Prolonged administration of U-73122 to p erifused frog adrenal explants markedly attenuated the ranakinin-evoke d stimulation of corticosterone and aldosterone secretion. Taken toget her, these data indicate that in the frog adrenal gland, ranakinin has no effect on the adenylyl cyclase system, but enhances polyphosphoino sitide hydrolysis. The stimulatory action of ranakinin on inositol pho sphate formation and corticosteroid secretion is mediated through acti vation of a phospholipase C positively coupled to a pertussis toxin-se nsitive G protein.