Role of cyclic nucleotides and calcium in the nutrient-induced release of cholecystokinin-like immunoreactivity in rats

J Physiol. 1992 Apr:449:37-48. doi: 10.1113/jphysiol.1992.sp019073.

Abstract

1. This study was undertaken with an isolated vascularly perfused rat duodenojejunal preparation to investigate the mechanisms of the release of cholecystokinin measured by immunoassay (cholecystokinin-like immunoreactivity, CCK-LI). 2. Intra-arterial infusion of forskolin (2-20 microM) evoked a prompt and well-sustained secretion of CCK-LI which was increased to a mean value of 600% of basal with the highest dose tested. 3-Isobutyl-1-methylxanthine (IBMX) (10(-6)-10(-4) M) stimulated the secretion of CCK-LI (maximal increase of 400% of basal at 10(-4) M). 3. Intra-arterial infusion of beta-phorbol 12-myristate 13-acetate (5 x 10(-7)-5 x 10(-6) M) and calcium ionophore A23187 (10(-6)-10(-5) M) alone or in combination provoked only a transient increase in the release of CCK-LI. 4. Luminal infusion of a 5% ovalbumin hydrolysate solution produced an immediate release of CCK-LI followed by a well-sustained secretion at 580% of basal. Intra-arterial infusion of IBMX (10(-5) or 10(-4) M) in combination with luminal peptone induced a release of CCK-LI which was equal to the sum of the CCK responses evoked by IBMX and peptone given separately. 5. Intra-arterial infusion of EGTA (2 mM) abolished the forskolin- and peptone-induced CCK secretion while luminal EGTA (2 mM) had no inhibitory effect. Verapamil (5 x 10(-5)-10(-4) M) or nifedipine (10(-5)-5 x 10(-5) M) inhibited the peptone-evoked CCK secretion. A high concentration of trifluoperazine (10(-4) M) strongly reduced the release of CCK-LI induced by intraluminal peptone while 10(-5) M was ineffective. 6. It is concluded that the peptone-induced secretion of CCK-LI involves a cyclic AMP-dependent mechanism and the activation of calcium channels possibly located at the basolateral side of the CCK cell.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Animals
  • Calcium / metabolism*
  • Calcium Channels / metabolism
  • Cholecystokinin / metabolism*
  • Colforsin / pharmacology
  • Dose-Response Relationship, Drug
  • Duodenum / metabolism
  • Jejunum / metabolism
  • Nucleotides, Cyclic / metabolism*
  • Radioimmunoassay
  • Rats
  • Receptors, Cholecystokinin / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Calcium Channels
  • Nucleotides, Cyclic
  • Receptors, Cholecystokinin
  • Colforsin
  • Cholecystokinin
  • Tetradecanoylphorbol Acetate
  • Calcium
  • 1-Methyl-3-isobutylxanthine