Residual inhibition of epidermal growth factor binding by pancreatic secretagogues and phorbol ester in rat pancreas

✍ Scribed by Murray Korc; Bruce E. Magun

• Publisher: John Wiley and Sons
• Year: 1985
• Tongue: English
• Weight: 496 KB
• Volume: 124
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041240226

✦ Synopsis

Cholecystokinin-octapeptide (CCG) inhibits 1251-labeled epidermal growth factor (EGF) cell-associated radioactivity in pancreatic acini, ostensibly as a result of its ability to mobilize cellular Ca2+. The phorbol ester tetradecanoyl phorbol acetate (TPA), a compound that activates protein kinase C, mimics the inhibitory action of CCG. 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 CCK8, reversed the inhibitory actions of CCG. Analysis of steady-state saturation kinetics of '251-EGF binding indicated that C C b 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 1251-EGF internalization. Removal of CCG 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 Ca2+, certain pancreatic secretagogues may also act through C-kinase to regualte EGF binding.