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.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002331:Carnitine / Q000031:analogs & derivatives*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010172:Palmitoylcarnitine / Q000494:pharmacology*; D010179:Pancreas / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D010172:Palmitoylcarnitine; D000001:Calcimycin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011493:Protein Kinase C; D002331:Carnitine; D002118:Calcium