Regulation of the serum-activated Ca(2+)-dependent chloride channel in Xenopus oocytes.

Fetal bovine serum evoked Ca(2+)-dependent chloride currents with two components in Xenopus oocytes. The evoked currents were inhibited by GDP beta S, but not by pertussis toxin (PTX). An inositol 1,4,5-triphosphate (IP3) receptor antagonist, heparin completely inhibited the currents, although a phospholipase C inhibitor, neomycin had no effect. The serum-activated currents were enhanced to 171% by a selective protein kinase C (PKC) inhibitor, GF109203X. By contrast, a potent PKC activator, TPA, abolished the initial component of the currents and arachidonic acid enhanced this effect. The effects of TPA and/or arachidonic acid on the currents inhibited by GF109203X. These results indicate that the receptor for serum is linked to a PTX-insensitive G-protein involving cytosolic Ca2+ release through IP3 and PKC activation by a mechanism independent of a phospholipase C-mediated phospholipid signaling. Furthermore, the evoked currents are regulated by PKC and arachidonic acid appears to potentiate its effect.