The interaction of caerulein with the rat pancreas. 3. Structural requirements for in vitro binding of caerulein-like peptides and its relationship to increased calcium outflux, adenylate cyclase activation, and secretion

Abstract

1. A comparison has been made of the ability of caerulein and caerulein analogs to compete with [3H]caerulein for binding to dispersed rat pancreatic acinar cells and to semi-purified rat pancreatic plasma membranes. A parallel study of the effect of such analogs on calcium outflux from isolated acinar cells, adenylate cyclase activity in pancreatic plasma membranes, and amylase secretion from pancreatic fragments was conducted. 2. In general, the biological potencies of caerulein analogs were proportional to their capacity to inhibit the binding of [3H]caerulein, which was interpreted as a reflection of the apparent affinity with which the various peptides interacted with hormone receptors. This comparison allows the conclusion that the C-terminal tetrapeptide of caerulein was sufficient for binding and for evoking the entire spectrum of biological activities. However, the presence of a tyrosyl sulfate residue in position 7 (from the C-terminal end) increased the affinity for the peptide substantially, and was also necessary for full efficiency for adenylate cyclase activation. 3. Dose-effect curves and previous data are compatible with the existence in pancreatic plasma membranes of spare receptors and of two-state receptors linked to two effector systems: a calcium ionophore and adenylate cyclase.