Mechanism of PGE inhibition of catecholamine release from adrenal medulla

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. 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.