Forskolin enhancement of acetylcholine-evoked cyclic AMP formation and catecholamine release in perfused dog adrenals.

Unstimulated efflux of cyclic AMP from perfused dog adrenal glands was not altered by 0.1 microM of forskolin and was slightly increased by 0.3 and 1.0 microM of forskolin. ACh stimulated efflux of cyclic AMP which preceded CA release and the efflux was dose-dependently enhanced by forskolin. Forskolin did not affect the spontaneous CA release but enhanced ACh-evoked catecholamine (CA) release. There was a close correlation between the dose relationship of forskolin enhancement of stimulated-cyclic AMP efflux and that of evoked-CA release. ACh-evoked CA release in the presence of forskolin was further potentiated by R020-1724, a phosphodiesterase inhibitor. CA release evoked by excess K+, or by caffeine in the presence or absence of external Ca2+ was also potentiated by forskolin. These results suggests that cyclic AMP generation may increase in response to stimulation of adrenal chromaffin cells and that the resulting increase of the nucleotide may function as a facilitating modulator of CA release.