tetragastrin and cholecystokinin-39

In a recent study it was demonstrated that the C-terminal octapeptide of cholecystokinin (CCK-26-33; often abbreviated CCK-8) and CCK-39 (= CCK--6-33) potently and with the same efficacy stimulated basal insulin secretion when injected intravenously to mice. In the present study, the effects of four other CCK fragments, CCK-30-33 (= CCK-4), CCK-1-33 (= CCK-33), CCK-1-21 (= CCK-21) and CCK-10-20, on basal and glucose-induced insulin secretion were studied. It was found that CCK-33 stimulated insulin secretion. At a dose level of 4.25 nmol/kg, plasma insulin concentrations were elevated by 58 +/- 7 microU/ml (P less than 0.001). On the contrary, neither CCK-4, nor CCK-21, nor CCK-10-20 displayed any effect on basal insulin secretion, not even at high dose levels. When injecting CCK-8, CCK-33 or CCK-39 at dose levels substimulatory on basal insulin secretion (0.53 nmol/kg), together with glucose, CCK-39 potentiated glucose-induced insulin secretion whereas CCK-8 and CCK-33 were without effects. In contrast, at the higher dose level of 5.3 nmol/kg, CCK-8, CCK-33, and CCK-39 all potentiated glucose-induced insulin secretion. The three other fragments, CCK-4, CCK-21, and CCK-10-20, were all without effects on glucose-induced insulin secretion. In conclusion, the potent stimulatory action on basal insulin secretion in the mouse exerted by various CCK fragments is confined to the C-terminal octapeptide (= CCK-8 or CCK-26-33).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cholecystokinin; Dose-Response Relationship, Drug; Female; Gastric Inhibitory Polypeptide; Glucose; Insulin; Insulin Secretion; Mice; Peptide Fragments; Sincalide; Tetragastrin

The effects of cholecystokinin (CCK) and gastrin on proximal and distal colonic motility were investigated because of the possible role of these peptides in feeding-induced colonic motility. Experiments were performed using 22 chloralose-urethane anaesthetized cats in which the colon was acutely denervated. The volume changes of the proximal and distal colon were recorded with water-filled flaccid balloons. The venous effluxes from the proximal and distal colon were recorded separately using drop recorder units. CCK-8, I-200 pmol X min-I close i.a., and pentagastrin, I-200 pmol X min-I close i.a., evoked dose-dependent contractions of the colon without altering systemic arterial blood pressure and colonic blood flow. The CCK peptides -8, -33 and -39 produced contractions of similar magnitude in the proximal and distal colon. The stimulatory effect of CCK-8 and pentagastrin on colonic motility was blocked by tetrodotoxin (I microgram X kg-I i.a.) and hexamethonium (I0 mg X kg-I i.v.). Atropine (0.5 mg X kg-I i.v.) completely blocked the responses to CCK-8 and pentagastrin in the distal colon but only partially in the proximal colon. Additional administration of naloxone (I mg X kg-I i.a.) abolished the remaining contractile response to the peptides in the proximal colon. The present results support the idea that CCK and pentagastrin have a stimulatory effect on distal colonic motility mediated via preganglionic and postganglionic cholinergic pathways. The possible role of opioid peptides and cholinergic mechanisms in the proximal colon is discussed.

Topics: Animals; Atropine; Cats; Cholecystokinin; Colon; Dose-Response Relationship, Drug; Female; Gastrointestinal Motility; Infusions, Intra-Arterial; Male; Naloxone; Pentagastrin; Peptide Fragments; Regional Blood Flow; Tetragastrin