Mechanism of PGE inhibition of catecholamine release from adrenal medulla

Abstract

Catecholamine (CA) secretion from the adrenal medulla was induced in vitro by acetylcholine (10 −4M) (ACh), by incubation in potassium-free medium, by addition of ouabain (10 −3 M), by theophylline (10 −2 M) or by salbutamol (10 −6 and 6 × 10 −6 M). Theophylline and salbutamol, but not ACh, released CA in a calcium-free medium supplemented with 2 mM EGTA. PGE 2 significantly inhibited both CA secretion evoked by ACh and that evoked by salbutamol, i.e. both secretion dependent on, and independent of, extracellular calcium. PGE 2 counteracted the increase of cAMP levels caused by ACh or salbutamol in adrenal medullary slices. PGE 2 also diminished the salbutamol-induced activation of adenylate cyclase in an adrenal medullary membrane preparation. PGE 2 reduced the rate of 45Ca efflux from slices of adrenal medulla preloaded with 45CaCl 2. It is suggested that PGE 2 inhibits CA secretion through the following sequence: inhibition of adenylate cyclase, a fall of cellular cAMP resulting in reduced release of calcium from intracellular binding sites and reduced free cytoplasmic calcium.