BACKGROUND/AIMS: It is generally believed that cholecystokinin (CCK) stimulates colonic motility, although there are controversial reports. It has also been suggested that postprandial peptide YY (PYY) release is CCK-dependent. Using a totally isolated, vascularly perfused rat colon, we investigated: (1) the roles of CCK and PYY on colonic motility, (2) to determine if CCK modulates PYY release from the colon to influence the motility and (3) to clarify whether the action of CCK and PYY on colonic motility is mediated via the influence of cholinergic input. METHODS: An isolated whole rat colon was used. Luminal pressure was monitored via microtip catheter pressure transducers from proximal and distal colon. After a control period, CCK-8 or PYY was administerd intraarterially with or without an anti-PYY serum, loxiglumide or atropine at 12, 60 and 240 pM. Each dose was given for a period of 15-minute and the contractile response was expressed as % changes over basal. PYY concentration in the portal effluent was determined by radioimmunoassay. RESULTS: Exogenous CCK-8 increased colonic motility which paralleled the increase in PYY release in the portal effluent. Exogenous PYY also significantly increased colonic motility although it was less potent than CCK. The stimulating effect of CCK-8 was significantly inhibited by an anti-PYY serum, and was completely abolished by loxiglumide, and almost completely abolished by atropine. CONCLUSIONS: CCK increases colonic motility via CCK1 receptor and it is mediated partly by PYY. Cholinergic input is required for the increased motility by either PYY or CCK.
Animals ; Atropine ; Catheters ; Cholecystokinin ; Colon ; Peptide YY ; Phenobarbital ; Proglumide ; Rats ; Sincalide ; Transducers, Pressure

BACKGROUND/AIMS: Prolactin (PRL) is essential for the lactating mammals, while cholecystokinin (CCK) does inhibit gastric emptying (GE). Present study attempted to determine whether both peptides interacted on the male rat GE, particularly the role of putative CCK1 receptor. METHODS: Acute hyperprolactinemia of male rats was induced by the intraperitoneal injection of ovine PRL (oPRL) in several divided doses 15 minutes before motility study. Rat chronic hyperprolactinemia was induced by the graft of 2 pituitary glands into the capsule of left kidney, while control rats received cerebral cortex graft only. Motility study was conducted 6 weeks later after graft surgery. Fifteen minutes after the intragastric feeding of radiochromium, rat was sacrificed to measure GE via the distribution of radioactivities within stomach and intestine. Among the CCK1 receptor blocking study using lorglumide, rats were divided to receive the regimens in terms of oPRL-vehicle plus lorglumide-vehicle, oPRL plus lorglumide-vehicle, oPRL-vehicle plus lorglumide and oPRL plus lorglumide. Plasma CCK level was measured using a homemade radioimmunoassay kit. RESULTS: Compared to vehicle treatment, acute hyperprolactinemic rats under highest dose (2.0 mg/kg) of oPRL treatment showed delayed GE (70.6% +/- 3.0% vs 42.1% +/- 6.6%, P < 0.05). Chronic hyperprolactinemic rats under graft surgery also showed inhibited GE (70.5% +/- 1.7% vs 54.5% +/- 4.7%, P < 0.05). Both models finally obtained elevated plasma CCK levels (P < 0.05). Lorglumide itself did not influence GE, however, delayed GE under oPRL treatment was restored following the concomitant lorglumide treatment. CONCLUSIONS: Our study suggests that PRL may delay male rat GE via a mechanism of endogenous CCK activation involving the peripheral CCK1 receptor.
Animals ; Cerebral Cortex ; Cholecystokinin ; Gastric Emptying ; Humans ; Hyperprolactinemia ; Injections, Intraperitoneal ; Intestines ; Kidney ; Male ; Mammals ; Peptides ; Pituitary Gland ; Plasma ; Proglumide ; Prolactin ; Radioactivity ; Radioimmunoassay ; Rats ; Stomach ; Transplants

The purpose of this study was to determine the effect of cholecystokinin octapeptide (CCK-8) on carotid sinus baroreflex in 36 anesthetized male rats by isolated carotid sinus perfusion in vivo. The results obtained are as follows. (1) By perfusion with CCK-8 (0.1, 0.5, 1.0 micromol/L), the functional curve of baroreflex was shifted to the right and upward, with a decrease in peak slope (PS) (p<0.001) and a reflex decrease (RD) in mean arterial pressure, while the threshold pressure (TP) and saturation pressure (SP) were significantly increased. Among the functional parameters of carotid sinus baroreflex, the changes in RD, PS and TP were dose-dependent. (2) Pretreatment with proglumide (100 micromol/L), a nonselective CCK receptor antagonist, the inhibitory effect of CCK-8 (0.5 micromol/L) on the baroreflex was significantly attenuated. (3) Pretreatment with L-NAME (100 micromol/L), an inhibitor of nitric oxide (NO) synthase, did not affect the inhibitory action of CCK-8 (0.5 micromol/L). (4) Preperfusion with Bay K 8644 (500 nmol/L), an agonist of calcium channel, could attenuate the effect of CCK-8 (0.5 micromol/L). It is suggested that the inhibitory action of CCK-8 on the baroreflex may be mediated by the activation of its receptors in the carotid sinus baroreceptor, leading to an inhibition of stretch-sensitive channels and a decrease in Ca(2+) influx. However, NO released from the endothelium seems not to be involved in the mechanism of this effect.
3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester ; pharmacology ; Animals ; Baroreflex ; drug effects ; Calcium Channel Agonists ; pharmacology ; Carotid Sinus ; physiology ; Depression, Chemical ; In Vitro Techniques ; Male ; NG-Nitroarginine Methyl Ester ; pharmacology ; Proglumide ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Sincalide ; pharmacology