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Residual inhibition of epidermal growth factor binding by pancreatic secretagogues and phorbol ester in rat pancreas
Author(s) -
Korc Murray,
Magun Bruce E.
Publication year - 1985
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041240226
Subject(s) - bombesin , cholecystokinin , epidermal growth factor , endocrinology , internalization , cholecystokinin receptor , medicine , protein kinase c , carbachol , receptor , chemistry , acinus , biology , pancreas , biochemistry , kinase , neuropeptide
Cholecystokinin‐octapeptide (CCK 8 ) inhibits 125 I‐labeled epidermal growth factor (EGF) cell‐associated radioactivity in pancreatic acini, ostensibly as a result of its ability to mobilize cellular Ca 2+ . The phorbol ester tetradecanoyl phorbol acetate (TPA), a compound that activates protein kinase C, mimics the inhibitory action of CCK 8 . In the present study we examined the relationship between occupancy of the cholecystokinin (CCK) receptor, the subsequent inhibition of EGF binding, and the potential role of C‐kinase activation in mediating this inhibition. Proglumide and dibutyryl cyclic GMP (dbGMP), two distinct competitive antagonists of CCK 8 , reversed the inhibitory actions of CCK 8 . Analysis of steady‐state saturation kinetics of 125 I‐EGF binding indicated that CCK 8 decreased the apparent affinity of the EGF receptor, mainly as a result of a marked decrease in the amount of internalized ligand. TPA also inhibited 125 I‐EGF internalization. Removal of CCK 8 and TPA from incubation medium did not abolish their inhibitory actions. Carbachol, but not bombesin, exerted a similar residual inhibitory effect. It is suggested that in addition to acting via Ca 2+ , certain pancreatic secretagogues may also act through C‐kinase to regulate EGF binding.