Inhibition of epidermal growth factor binding in rat pancreatic acini by palmitoyl carnitine: evidence for Ca2+ and protein kinase C independent regulation.

D,L-Palmitoyl carnitine (PC), an inhibitor of protein kinase C, decreased [125I]epidermal growth factor (EGF) cell-associated radioactivity in rat pancreatic acini. H-7, another inhibitor of protein kinase C, failed to inhibit [125I]EGF binding. Palmitate, carnitine, acetylcarnitine, and 2-tetradecylglycidic acid methyl ester (a specific inhibitor of endogenous PC formation) did not alter [125I]EGF binding. PC conjugated to bovine serum albumin (PC-BSA) decreased [125I]EGF cell-associated radioactivity to the same extent as PC. Neither compound affected the distribution of cell-associated radioactivity into acid-resistant and acid-dissociable compartments. In contrast, cholecystokinin octapeptide (CCK8) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) markedly inhibited the distribution of [125I]EGF into the acid-resistant compartment. Proglumide, a competitive antagonist of CCK8, reversed the inhibitory action of CCK8 but not that of PC-BSA. PC-BSA did not inhibit [125I]insulin binding, and did not enhance amylase release, a Ca2+-mediated effect. Further, its inhibitory effect on [125I]EGF cell-associated radioactivity was not additive with the inhibitory effect of the calcium ionophore A23187. Both PC-BSA and H-7 inhibited Ca2+- and phospholipid-dependent kinase activity in soluble and particulate fractions when added to disrupted acini, but in the particulate compartment only when added to intact acini. These findings suggest that PC-BSA may regulate EGF binding via a novel mechanism that is independent of protein kinase C activation or Ca2+ mobilization.