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

Murray Korc, B. E. Magun

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Cholecystokinin-octapeptide (CCK8) inhibits 125I-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 CCK8. 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 CCK8. Analysis of steady-state saturation kinetics of 125I-EGF binding indicated that CCK8 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 125I-EGF internalization. Removal of CCK8 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 regulate EGF binding.

Original languageEnglish (US)
Pages (from-to)344-348
Number of pages5
JournalJournal of Cellular Physiology
Volume124
Issue number2
StatePublished - 1985
Externally publishedYes

Fingerprint

Phorbol Esters
Epidermal Growth Factor
Rats
Pancreas
Acetates
Dibutyryl Cyclic GMP
Phosphotransferases
Proglumide
Cholecystokinin Receptors
Bombesin
Sincalide
Radioactivity
Carbachol
Epidermal Growth Factor Receptor
Protein Kinase C
Chemical activation
Ligands
Kinetics
phorbol

ASJC Scopus subject areas

  • Cell Biology
  • Clinical Biochemistry
  • Physiology

Cite this

Residual inhibition of epidermal growth factor binding by pancreatic secretagogues and phorbol ester in rat pancreas. / Korc, Murray; Magun, B. E.

In: Journal of Cellular Physiology, Vol. 124, No. 2, 1985, p. 344-348.

Research output: Contribution to journalArticle

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