ACTIVATION OF NA-ADENOMA CELLS BY PACAP( CHANNELS IN GH(3) CELLS AND HUMAN PITUITARY)

The effects of pituitary adenylate cyclase activating polypeptide (PAC AP) on ion channels were examined in GH(3) cells and human pituitary a denoma cells. In GH(3) cells, PACAP-38 (10-9 M) reversibly activated t etrodotoxin-sensitive Na+ channels but had little effect on nicardipin e-sensitive Ca2+ channels. PACAP-induced increase in Na+ currents was inhibited by PACAP(6-38), a specific PACAP receptor antagonist, and Rp -cAMPs, an inhibitor for protein kinase A, and mimicked by 8-bromo-cAM P. In human pituitary adenoma cells, PACAP also activated tetrodotoxin -sensitive Na+ channels and growth hormone secretion. These results su ggest the possibility that PACAP can activate voltage-gated Na+ channe ls via adenylate cyclase-protein kinase A pathway in the pituitary. (C ) 1997 Elsevier Science Inc.