ENTRY OF EXTRACELLULAR CALCIUM MEDIATES DOPAMINE D1-STIMULATED GROWTH-HORMONE RELEASE FROM GOLDFISH PITUITARY-CELLS

Unlike mammals, the goldfish is unique in having dopamine (DA) D1 rece ptors in the anterior pituitary. In this species, DA stimulates growth hormone (GH) release via D1 receptors coupled to the cAMP-dependent p athway. To further examine the postreceptor mechanisms of this novel p ituitary DA D1 system, the role of extracellular Ca2+ ([Ca2+](e)) in m ediating DA D1-stimulated GH release was studied using dispersed goldf ish pituitary cells. The GH responses to DA (1 nM-10 mu M), the D1 ago nist SKF38393 (1 mu M), and the Ca2+ ionophore A23187 (10 mu M) were a bolished by incubation with Ca2+-deficient medium. Incubation with dep olarizing doses of KCl (10-25 mM), which activate voltage-sensitive Ca 2+ channels (VSCC), induced GH release in a dose-dependent manner. In contrast, the VSCC blockers nifedipine (10 mu M), nicardipine (10 mu M ), and verapamil (10 mu M) and the inorganic competitor of Ca2+ entry CoCl2 (5 mM) blocked the GH responses to DA (1 mu M) as well as SKF383 93 (1 mu M). These results strongly indicate that the entry of [Ca2+]( e) via VSCC is an essential part of the signal transduction mechanisms mediating DA D1-stimulated GH release in the goldfish. In this study, the possible interactions between the Ca2+- and cAMP-dependent pathwa ys in DA-induced GH secretion were also investigated. The membrane-per meant cAMP analogue sBr.cAMP (1 mM) and the adenylate cyclase activato r forskolin (10 mu M) stimulated GH release from goldfish pituitary ce lls. These GB responses were suppressed by incubation with Ca2+-defici ent medium or with the VSCC blocker nifedipine (10 mu M). Furthermore, the GH responses to forskolin (10 mu M) and the nonselective DA agoni st apomorphine (1 mu M) were not additive to that of the Ca2+ ionophor e A23187 (10 mu M). These results suggest that [Ca2+](e) entry induced by DA D1 stimulation occur at steps after activation of the cAMP-depe ndent pathway. (C) 1994 Academic Press, Inc.