Cholecystokinin receptor occupation and cholecystokinin-induced calcium mobilization in the early phase in rat pancreatic acini

Biochim Biophys Acta. 1991 Sep 3;1094(2):231-7. doi: 10.1016/0167-4889(91)90014-o.

Abstract

We examined receptor occupation, calcium mobilization and amylase release for cholecystokinin octapeptide (CCK-8) within a 3-min incubation period at 37 degrees C using dispersed acini from rat pancreas. Analysis of competitive binding inhibition data obtained after a 3-min incubation revealed the presence of only a single class of CCK receptors, while two classes of CCK receptor, i.e., high-affinity and low-affinity CCK receptors, were detected when binding reached a steady-state after a 60-min incubation. The IC50 of CCK receptors calculated from the 3-min binding data was 19.0 +/- 0.5 nM (mean +/- S.D.), close to the Kd of the low-affinity CCK receptors determined by equilibrium binding studies. Exposure of fura-2-loaded acini to 10-1000 pM CCK-8 caused an immediate and dose-dependent increase in [Ca2+]i followed by a gradual decrease in [Ca2+]i. The CCK-stimulated amylase release after 3 min of incubation was biphasic; amylase release increased over the dose range of 3-300 pM CCK-8, peaked at 300 pM CCK-8 and decreased with supramaximal concentrations of CCK-8. Our data suggest that occupation of the low-affinity, but not the high-affinity, CCK receptors is more directly associated with calcium mobilization and subsequent stimulation of amylase release in rat pancreatic acini.

MeSH terms

  • Amylases / metabolism
  • Animals
  • Calcium / metabolism*
  • Cholecystokinin / pharmacology*
  • Dose-Response Relationship, Drug
  • In Vitro Techniques
  • Male
  • Pancreas / metabolism*
  • Rats
  • Receptors, Cholecystokinin / metabolism*
  • Time Factors

Substances

  • Receptors, Cholecystokinin
  • Cholecystokinin
  • Amylases
  • Calcium