Mechanism of PGE inhibition of catecholamine release from adrenal medulla

Catecholamine (CA) secretion from the adrenal medulla was induced in vitro by acetylcholine (10(-4)M) (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 x 10(-6) M). Theophylline and salbutamol, but not ACh, released CA in a calcium-free medium supplemented with 2mM EGTA. PGE2 significantly inhibited both CA secretion evoked by ACh and that evoked by salbutamol, i.e. both secretion dependent on, and independent of, extracellular calcium, PGE2 counteracted the increase of cAMP levels caused by ACh or salbutamol in adrenal medullary slices. PGE2 also diminished the salbutamol-induced activation of adenylate cyclase in an adrenal medullary membrane preparation, PGE2 reduced the rate of 45Ca efflux from slices of adrenal medulla preloaded with 45CaCl2. It is suggested that PGE2 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.