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

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.