Previously, we have demonstrated that dopamine (DA) stimulates growth hormone (GH) release from the goldfish pituitary through DA D1 receptors. In the present study, the role of cAMP in DA D1-stimulated GH release was investigated using static incubation of goldfish pituitary cells. The D1 agonist SKF38393 (1 nM-10 microM) induced GH release and cAMP accumulation in a dose-dependent manner with ED50s of 73 +/- 32 and 109 +/- 53 nM, respectively. In contrast, the D2 agonist LY171555 (1 nM-10 microM) was not effective in these regards. The GH-releasing action of SKF38393 was mimicked by the adenylate cyclase activator forskolin (0.1-40 microM) as well as the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.1 microM-1 mM). Dideoxyforskolin (0.1-40 microM), a derivative of forskolin inactive in stimulating adenylate cyclase, did not affect basal GH secretion. Similar stimulatory effects on GH release were also observed using the membrane-permeant cAMP analogs (10 microM-2 mM), dibutyryl cAMP and 8-bromo cAMP (8Br.cAMP). In the presence of a high dose (1 mM) of Br.cAMP, the ability of SKF38393 (1 nM-10 microM) to stimulate GH release was abolished, suggesting that the GH-releasing actions of cAMP and DA D1 stimulation are mediated through a common signal transduction mechanism. In the present study, the possible involvement of the cAMP-dependent enzyme protein kinase A (PKA) in DA D1-stimulated GH release was also examined. The GH responses to 8Br.cAMP (1 mM) and SKF38393 (1 microM) were blocked by simultaneous treatment with the PKA inhibitor H89 (10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
