PACAP MODULATES L-TYPE CA2-MUSCLE CELLS - INVOLVEMENT OF PKC AND PKA(CHANNEL CURRENTS IN VASCULAR SMOOTH)

he effect of pituitary adenylate cyclase activating polypeptide (PACAP ) on the L-type Ca2+ channel current (L-channel current) was studied i n smooth muscle cells prepared from the rat tail artery, PACAP caused an increase in the amplitude of the L-channel current, The maximal inc rease (56%) occurred at a PACAP concentration of 1 x 10(-8) M; higher concentrations resulted in a smaller increase, Investigation into the intracellular mechanisms of PACAP action revealed that the increase in L-channel currents was blocked by calphostin C and bisindolylmaleimid e IV [protein kinase C (PKC) inhibitors] and mimicked by 4 beta-phorbo l 12-myristate 13-acetate (PMA), an activator of PKC, PACAP was also f ound to cause translocation of PKC, suggesting that the increase in th e current by PACAP was due to PKC. In contrast, activation of cAMP-dep endent protein kinase (PKA) by 8-bromo-cAMP caused an inhibition of th e L-channel current. A high concentration of PACAP (1x10(-6) M) had no effect on the L-channel current, The null effect of PACAP on the L-ch annel current could be converted to an increase by Rp-cAMPs, a cAMP an tagonist, and a decrease by calphostin C. PACAP also increased cAMP ac cumu lation. These observations indicate the effect of PACAP on the L- channel current represents the integration of two signaling mechanisms that involve the activation of PKA and PKC.