Cytosolic calcium regulates epidermal growth factor endocytosis in rat pancreas and cultured fibroblasts.
Cholecystokinin octapeptide (CCK8), the COOH-terminal moiety of cholecystokinin (CCK), exerted a rapid inhibitory effect on total cell-associated 125I-labeled epidermal growth factor (125I-EGF) binding by decreasing the rate of EGF internalization in isolated rat pancreatic acini. Removal of CCK8 from incubation medium followed by extensive washing of acini did not abolish its inhibitory effect, indicating that its action was not readily reversible. Proglumide, a competitive antagonist of CCK8, blocked the inhibitory action of the secretagogue. Addition of CCK8 to cells previously exposed to 125I-EGF did not enhance the release of cell-associated 125I activity. CCK8 did not inhibit the binding of 125I-labeled insulin to pancreatic acini. Other pancreatic secretagogues that enhance digestive-enzyme release through Ca2+, including caerulein, bombesin, carbachol, gastrin, and the Ca2+ ionophore A23187, also inhibited cell-associated 125I-EGF radioactivity. Further, at 37 degrees C the ionophore A23187 inhibited specific 125I-EGF binding in human A-431 carcinoma cells, Swiss 3T3 cells, and Rat-1 fibroblasts, and this effect was abolished when 125I-EGF internalization was reduced by incubating cells at 4 degrees C. It is concluded that alterations in cellular Ca2+ in the pancreas and other cells lead to inhibition of EGF endocytosis.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D003600:Cytosol / Q000502:physiology; D004705:Endocytosis; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors; D005347:Fibroblasts / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism*; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology*; D012844:Sincalide / Q000494:pharmacology; D013696:Temperature
D007328:Insulin; D011956:Receptors, Cell Surface; D000001:Calcimycin; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D011972:Receptor, Insulin; D012844:Sincalide; D002118:Calcium