Inhibition of Epidermal Growth Factor Binding in Rat Pancreatic Acini by Palmitoyl Carnitine: Evidence for Ca²⁺ and Protein Kinase C Independent Regulation¹ Free

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.