Analysis of the effect of pituitary adenylate cyclase-activating polypeptide (PACAP) on growth hormone (GH) secretion in GH3 cells

We examined the effects of PACAP on growth hormone (GH) secretion, intracellular Ca2+ concentrations ([Ca2+]i) and ion channels in GH3 cells. PACAP-38 and vasoactive intestinal polypeptide (VIP) (10−9M) increased GH secretion. PACAP-induced increase in GH secretion was inhibited by PACAP(6–38), a PACAP antagonist. PACAP-38 (10−10M) increased [Ca2+]; in GH3 cells. The increase in [Ca2+]; was inhibited by 1) PACAP(6–38) (10−6M), 2) nicardipine (10−5M), a Ca2+ channel blocker, 3) depletion of extracellular Ca2+ or 4) tetrodotoxin (3x10−7M), a Na+ channel blocker. Na+ channel currents were increased by PACAP, whereas Ca2+ channel currents were unchanged. 8-bromo-cAMP (10−3M) increased [Ca2+]i and Rp-cAMPS (10−3M), an inhibitor for protein kinase A, eliminated PACAP-induced increase in [Ca2+]i. Thus the present study suggests that PACAP activates Na+ channels via cAMP-protein kinase A system coupled with its receptor to depolarize membrane potential, which in turn activates Ca2+ channels to induce an increase in [Ca2+]i, a trigger for GH secretion.