PT  - JOURNAL ARTICLE
AU  - Brockenbrough, J. Scott
AU  - Korc, Murray
TI  - Inhibition of Epidermal Growth Factor Binding in Rat Pancreatic Acini by Palmitoyl Carnitine: Evidence for Ca<sup>2+</sup> and Protein Kinase C Independent Regulation
DP  - 1987 Apr 01
TA  - Cancer Research
PG  - 1805--1810
VI  - 47
IP  - 7
4099  - http://cancerres.aacrjournals.org/content/47/7/1805.short
4100  - http://cancerres.aacrjournals.org/content/47/7/1805.full
SO  - Cancer Res1987 Apr 01; 47
AB  - 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. ©1987 American Association for Cancer Research.