Involvement of different mechanisms in the stimulatory effects of cholecystokinin octapeptide on gastrointestinal and colonic motility in dogs.
The effects of an intravenous infusion of cholecystokinin octapeptide (CCK-8, 1 microgram.kg-1.h-1) were investigated in conscious fasted dogs chronically fitted with strain-gauge transducers on the antrum, the jejunum, and the colon. Attempts to antagonize the increase of motility appearing at the three levels during CCK infusion were made using different blockers to elucidate the mechanisms involved. Asperlicin (a specific CCK antagonist) blocked the effects of CCK-8 at the three levels, while atropine and somatostatin were only effective in the jejunum and colon. Methyl-levallorphan (a mu-opiate antagonist that poorly crosses the blood-brain barrier) antagonized the CCK-induced colonic stimulation when intracerebroventricularly administered. Serotonin, histamine, substance P, and K-antagonists as well as a benzodiazepine did not modify the CCK-8 induced stimulation. It was concluded that the stimulatory effect of CCK-8 resulted from (a) a direct stimulation of the smooth muscle cells at gastric level, (b) a cholinergic activation of the jejunum and the colon, and (c) the involvement of a mu-opioid central component in the colonic response only.
Fargeas
M J
MJ
Department of Pharmacology, Institut national de la recherche agronomique, Toulouse, France.
Bassotti
G
G
Fioramonti
J
J
Bueno
L
L
D000818:Animals; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology; D003106:Colon / Q000187:drug effects; D004285:Dogs; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006633:Histamine Antagonists / Q000494:pharmacology; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology; D012844:Sincalide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013268:Stimulation, Chemical
D001570:Benzodiazepinones; D006633:Histamine Antagonists; D009292:Narcotic Antagonists; D010276:Parasympatholytics; D012702:Serotonin Antagonists; D012844:Sincalide; C046367:asperlicin