Cyclic AMP Modulates Differentially the Release of Dopamine Induced by Hypoxia and Other Stimuli and Increases Dopamine Synthesis in the Rabbit Carotid Body

We have investigated the effects of different treatments that increase cyclic AMP levels on the in vitro synthesis and release of catecholamines in the rabbit carotid body. We also measured the rate of 45Ca2+ efflux from previously loaded carotid bodies under different conditions. Forskolin produced a dose-dependent increase in the release of [3H]dopamine elicited by a hypoxic stimulus of medium intensity (PO2 = 33 mm Hg) without altering basal [3H]dopamine release (100% O2-equilibrated medium). At a concentration of 5 x 10(-6) M, forskolin increased the release of [3H]dopamine induced by hypoxic stimuli of different intensities; the increase was maximal (498%) at the lowest intensity of hypoxic stimuli (PO2 = 66 mm Hg), averaged 260% for hypoxic stimuli of intermediate intensity and 2 x 10(-4) M cyanide, and was 150% under anoxia. Dibutyryl cyclic AMP (2 mM) and 3-isobutyl-1-methylxanthine (0.5 mM) mimicked forskolin effects under hypoxic stimulation. Forskolin (5 x 10(-6) M) also increased (180%) the release of [3H]dopamine induced by 20% CO2/pH 6.6, 2.5 x 10(-4) M dinitrophenol, and 3 x 10(-5) M ionomycin. Forskolin and 3-isobutyl-1-methylxanthine were without effect on the release of [3H]dopamine elicited by 30 mM extracellular K+. Forskolin (5 x 10(-6) M) augmented significantly the rate of 45Ca2+ efflux induced by hypoxic stimuli (PO2 of 33 and 66 mm Hg) and 2 x 10(-4) M cyanide and showed a tendency to increase (20%) the 45Ca2+ efflux induced by dinitrophenol and low pH and to decrease (21%) the efflux induced by 30 mM K+ without altering the rate of efflux under basal conditions.(ABSTRACT TRUNCATED AT 250 WORDS)