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Effects of CCK‐receptor antagonist on colonic motor activity in dogs
Author(s) -
KARAUS M.,
NIEDERAU C.
Publication year - 1995
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.1995.tb00210.x
Subject(s) - medicine , endocrinology , cholecystokinin , antagonist , postprandial , cholecystokinin receptor , gastrointestinal hormone , bolus (digestion) , chemistry , peptide hormone , receptor , insulin
This study employed a cholecystokinin (CCK) antagonist to evaluate whether endogenous CCK regulates fasted and fed motor patterns of the colon. Experiments were performed in six conscious dogs, each in duplicate. Motor activity was recorded by four strain gauge transducers implanted on the colon. The effects of the CCK‐analogue caerulein and the CCK‐antagonist loxiglumide (Rotta, Italy) were studied in fasted and fed states. The motor activity was computed for the area under contractions. Caerulein given as an intravenous bolus of 50 ng kg −1 during a quiescent state caused a burst of phasic and tonic contractions resembling a regular non‐migrating motor complex. Physiological doses of 10 ng kg −1 caerulein, which increases plasma CCK‐immunoreactivity to postprandial levels, had no effect. Continuous intravenous infusion of 10 mg kg −1 h −1 loxiglumide completely abolished the effects of 50 ng kg −1 caerulein. The motor activity stimulated by the cholinesterase inhibitor neostigmine (10 μg kg −1 ) was not altered by loxiglumide. Loxiglumide given in the fasted state reduced the area under contractions in the proximal colon by 26.8 ± 12.8% compared to the control without loxiglumide (P < 0.05). The postprandial increase in motor activity in the distal colon, the gastrocolonic response, was significantly inhibited by loxiglumide. Moreover, loxiglumide reduced the area under 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 results show that loxiglumide acts as a specific antagonist of the actions of CCK on colonic motor activity in the dog. Only supraphysiological concentrations of caerulein affect colonic motor activity. Loxiglumide, at a dose which abolishes the effects of exogenous CCK, significantly decreases fasting motor activity in the proximal colon. Loxiglumide also significantly reduces colonic motor activity after a meal. Therefore, CCK plays a physiological role in the regulation of fasting and fed motor activity of the canine colon as a neurotransmitter but not as a hormone.