Mechanism of action of cholecystokinin octapeptide on cat lower esophageal sphincter.
In five cats we examined 1) the role of a cholinergic mechanism in cholecystokinin octapeptide (CCK-OP) excitation of the lower esophageal sphincter (LES) and 2) the interaction between CCK-OP-induced excitation and inhibition of the LES. Under ketamine anesthesia, LES pressure was monitored with a sleeve catheter. With CCK-OP, LES excitation was seen in four of five cats, and inhibition was seen in three of five cats. (4-Hydroxy-2-butynyl)trimethylammonium chloride (McNeil-A343) produced similar responses in the same cats but was less potent than CCK-OP. Atropine and/or hexamethonium reduced the response to CCK-OP. Pirenzepine had no effect on any CCK-OP response but reduced relaxation and enhanced excitation produced by McNeil-A343. Phentolamine increased CCK-OP-induced relaxation. In conclusion, CCK-OP can produce LES contraction through a preganglionic cholinergic mechanism involving a nicotinic synapse; however, induction of relaxation occurs predominantly at a postganglionic site involving adrenergic modulation. There is animal-to-animal variability in the balance of excitatory and inhibitory mechanisms to the LES, which determines the effect of a drug capable of activating both mechanisms.
Salapatek
A M
AM
Department of Medicine, University of Toronto, Ontario, Canada.
Hynna-Liepert
T
T
Diamant
N E
NE
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D000818:Animals; D002415:Cats; D004943:Esophagogastric Junction / Q000187:drug effects*; D005260:Female; D008297:Male; D010276:Parasympatholytics / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011312:Pressure; D012844:Sincalide / Q000494:pharmacology*
D010276:Parasympatholytics; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D012844:Sincalide; D010646:Phentolamine