EFFECTS OF CCK-RECEPTOR ANTAGONIST ON COLONIC MOTOR-ACTIVITY IN DOGS

This study employed a cholecystokinin (CCK) antagonist to evaluate whe ther endogenous CCK regulates fasted and fed motor patterns of the col on. Experiments were performed in six conscious dogs, each in duplicat e. Motor activity was recorded by four strain gauge transducers implan ted on the colon. The effects of the CCK-analogue caerulein and the CC K-antagonist loxiglumide (Rotta, Italy) were studied in fasted and fed states. The motor activity was computed for the area under contractio ns. Caerulein given as an intravenous bolus of 50 ng kg(-1) during a q uiescent state caused a burst of phasic and tonic contractions resembl ing a regular non-migrating motor complex. Physiological doses of 10 n g kg(-1) caerulein, which increases plasma CCK-immunoreactivity to pos tprandial levels, had no effect. Continuous intravenous infusion of 10 mg kg(-1) h(-1) loxiglumide completely abolished the effects of so ng kg(-1) caerulein. The motor activity stimulated by the cholinesterase inhibitor neostigmine (10 mu g kg(-1)) was not altered by loxiglumide . Loxiglumide given in the fasted state reduced the area under contrac tions in the proximal colon by 26.8 +/- 12.8% compared to the control without loxiglumide (P < 0.05). The postprandial increase in motor act ivity in the distal colon, the gastrocolonic response, was significant ly inhibited by loxiglumide. Moreover, loxiglumide reduced the area un der contractions in the fed state by 25.4 +/- 10.7% and 19 +/- 7.2% in the proximal and distal colon, respectively (P < 0.05). The present r esults show that loxiglumide acts as a specific antagonist of the acti ons of CCK on colonic motor activity in the dog. Only supraphysiologic al concentrations of caerulein affect colonic motor activity. Loxiglum ide, at a dose which abolishes the effects of exogenous CCK, significa ntly decreases fasting motor activity in the proximal colon. Loxiglumi de also significantly reduces colonic motor activity after a meal. The refore, CCK plays a physiological role in the regulation of fasting an d fed motor activity of the canine colon as a neurotransmitter but not as a hormone.