Reflex gastric motor inhibition caused by intraperitoneal bradykinin: antagonism by Hoe 140, a bradykinin antagonist.
Bradykinin (BK) has been reported to have mixed excitatory/inhibitory effects on gastrointestinal motility. The present study examined the mechanism responsible for the inhibition of gastric motor activity caused by intraperitoneal administration of BK. Gastric motor activity was measured by recording the intragastric pressure (IGP) of phenobarbital-anesthetized rats via a transesophageal catheter. To facilitate the study of inhibitory influences, gastric motility was stimulated by neurokinin A (NKA), which on intravenous injection evoked reproducible gastric contractions as measured by a rise of IGP. Intraperitoneal injection of BK (0.1-10 nmol) inhibited the NKA-induced increase in IGP in a dose-dependent manner, and the effect of epigastric administration of BK was not significantly different from that of intraperitoneal administration. The inhibitory effect of intraperitoneal BK on gastric motility was due to an effect on BK2 receptors because it was blocked by prior intraperitoneal injection of the BK2 antagonist Hoe 140. The specificity of this BK antagonist was demonstrated by its inability to antagonize the effect of intraperitoneal hydrochloric acid (HCl), which, like BK, inhibited the NKA-induced gastric contractions. Because the BK- and HCl-induced inhibition of the NKA-induced rise of IGP was abolished by acute removal of the celiac-superior mesenteric ganglion complex, but left unaltered by acute bilateral subdiaphragmatic vagotomy, it is inferred that intraperitoneal BK inhibits gastric motor activity via activation of an autonomic reflex that involves prevertebral ganglia.
Holzer
P
P
University of Graz, Department of Experimental and Clinical Pharmacology, Austria.
D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005260:Female; D005728:Ganglia, Sympathetic / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006851:Hydrochloric Acid / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D008297:Male; D015288:Neurokinin A / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D013270:Stomach / Q000187:drug effects; D014630:Vagus Nerve / Q000502:physiology
C065679:icatibant; D015288:Neurokinin A; D006851:Hydrochloric Acid; D001920:Bradykinin