CYCLIC 3',5'-ADENOSINE-MONOPHOSPHATE MEDIATES DOPAMINE D1-STIMULATED GROWTH-HORMONE RELEASE FROM GOLDFISH PITUITARY-CELLS

Previously, we have demonstrated that dopamine (DA) stimulates growth hormone (GH) release from the goldfish pituitary through DA D1 recepto rs. In 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 mu M) induced GH release and cAMP acc umulation in a dose-dependent manner with ED(50s) of 73 +/- 32 and 109 +/- 53 nM, respectively. In contrast, the D2 agonist LY171555 (1 nM-1 0 mu M) was not effective in these regards. The GH-releasing action of SKF38393 was mimicked by the adenylate cyclase activator forskolin (0 .1-40 mu M) as well as the phosphodiesterase inhibitor 3-isobutyl-1-me thylxanthine (0.1 mu M-1 mM). Dideoxyforskolin (0.1-40 mu M), a deriva tive of forskolin inactive in stimulating adenylate cyclase, did not a ffect basal GH secretion. Similar stimulatory effects on GH release we re also observed using the membrane-permeant cAMP analogs (10 mu M-2 m M), dibutyryl cAMP and 8-bromo cAMP (8Br.cAMP). In the presence of a h igh dose (1 mM) of Br.cAMP, the ability of SKF38393 (1 nM-10 mu M) to stimulate GH release was abolished, suggesting that the GH-releasing a ctions of cAMP and DA D1 stimulation are mediated through a common sig nal transduction mechanism. In the present study, the possible involve ment of the cAMP-dependent enzyme protein kinase A (PKA) in DA D1-stim ulated GH release was also examined. The GH responses to 8Br.cAMP (1 m M) and SKF38393 (1 mu M) were blocked by simultaneous treatment with t he PKA inhibitor H89 (10 mu M). The same dose (10 mu M) of H89 did not affect the GH response to the protein kinase C activator sn-1,2-dioct anoyl glycerol (0.1 mM), indicating that this inhibitor is selective t o PKA in the goldfish. Taken together, the present study provides evid ence that DA D1-stimulated GH release from goldfish pituitary cells is mediated through the adenylate cyclase-cAMP-PKA pathway.