Direct modulation of epidermal growth factor binding by cholecystokinin.
The effects of cholecystokinin-octapeptide (CCK8), the biologically active C-terminal moiety of cholecystokinin (CCK), on the binding of epidermal growth factor (EGF) were studied in isolated rat pancreatic acini. CCK8 inhibited 125I-EGF binding in a dose-dependent manner. One-half maximal inhibition occurred at 5 X 10(-10)M, and maximal inhibition at 10(-8)M CCK8. This inhibitory effect was detectable within 5 minutes of addition of CCK8, and was not associated with enhanced degradation of 125I-EGF in incubation media. Unlabeled EGF exerted only a slightly greater inhibitory effect than CCK8 on 125I-EGF binding at equivalent molar concentrations. In contrast to CCK8, the gastrointestinal hormone vasoactive intestinal polypeptide (VIP) did not significantly alter EGF binding. CCK8 also inhibited EGF binding in mouse pancreatic acini, but did not alter binding in A-431 human carcinoma cells. These findings suggest that physiological levels of CCK may regulate EGF binding in the pancreas and other tissues with receptors for both hormones. They thus point to a previously unrecognized mechanism for hormonal interaction.
D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell; D002460:Cell Line; D002766:Cholecystokinin / Q000494:pharmacology*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D012844:Sincalide; D014846:Vulvar Neoplasms
D001067:Appetite Depressants; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D004815:Epidermal Growth Factor; D002766:Cholecystokinin; D066246:ErbB Receptors; D012844:Sincalide