Cholecystokinin and nitric oxide in transient lower esophageal sphincter relaxation to gastric distention in dogs.
OBJECTIVE
Transient lower esophageal sphincter relaxations have been found to be involved in gastroesophageal reflux. The purpose of this study was to determine whether cholecystokinin (CCK) and nitric oxide are involved in the occurrence of these relaxations.


METHODS
Pharyngeal, esophageal, lower esophageal sphincter, and gastric pressures were monitored in five dogs through a cervical esophagostomy. Gastric distentions with air, at a constant pressure of 1.56 kPa, were performed for 30-minute sessions using a barostat.


RESULTS
During gastric distention at 1.56 kPa, transient relaxations occurred at a mean rate of 7.2 +/- 0.6 every 30 minutes. CCK-8 infused intravenously (0.1-1 microgram.kg-1.h-1) dose dependently increased the occurrence of relaxations while it was reduced by the CCK-A receptor antagonist devazepide but not the CCK-B antagonist L365260, both administered intravenously in a dose range of 0.1-100 micrograms/kg. The two antagonists administered intracerebroventricularly (1 microgram/kg) did not modify the occurrence of relaxations. Both devazepide and L365260 (10 micrograms/kg) reduced the CCK-induced relaxations, but devazepide was more potent. The nitric oxide synthase inhibitor NG-nitro-L-arginine-methyl ester (20 mg/kg) reduced the number of relaxations during gastric distention in the presence or absence of CCK infusion. This effect was reversed by L-arginine but not D-arginine (200 mg/kg).


CONCLUSIONS
CCK is involved in the occurrence of transient lower esophageal sphincter relaxations through peripheral CCK-A receptors and an L-arginine nitric oxide pathway.
Boulant
J
J
Department of Pharmacology, Institut National de Recherche Agronomique, Toulouse, France.
Fioramonti
J
J
Dapoigny
M
M
Bommelaer
G
G
Bueno
L
L
D000388:Air; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002766:Cholecystokinin / Q000502:physiology*; D004285:Dogs; D004943:Esophagogastric Junction / Q000502:physiology*; D009126:Muscle Relaxation; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D011312:Pressure; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000145:classification; D012844:Sincalide / Q000494:pharmacology; D013270:Stomach / Q000502:physiology*; D013997:Time Factors
D011949:Receptors, Cholecystokinin; D009569:Nitric Oxide; D002766:Cholecystokinin; D001120:Arginine; D012844:Sincalide; D019331:NG-Nitroarginine Methyl Ester