Role of capsaicin-sensitive afferent neurons in receptive relaxation induced by gastric distension in rats.
We investigated the role of capsaicin-sensitive afferent neurons in receptive relaxation of the rat stomach in response to distension. Under urethane anesthesia, a balloon with barostat was inserted through the pylorus and placed in the forestomach. Isobaric distension was performed in a stepwise increment of 2 mmHg, each lasting for 2 min, while the corresponding intragastric volume was recorded. Gastric distension produced the intraballoon volume in a progressive manner with saturation, suggesting the occurrence of receptive relaxation of the stomach during distension. Intragastric application of capsaicin significantly enhanced the degree of receptive relaxation. The capsaicin-induced enhancement of receptive relaxation was totally abolished by bilateral vagotomy as well as chemical ablation of capsaicin-sensitive afferent neurons. Likewise, the enhanced receptive relaxation in response to stomach distension was also significantly attenuated by pretreatment of the animals with NG-nitro-L-arginine methyl ester (L-NAME, an inhibitor of nitric oxide (NO) synthase), calcitonin gene related peptide (CGRP)8-37 (CGRP antagonist), indomethacin and ONO-8711 (EP1 receptor antagonist). These results suggest that capsaicin significantly enhanced the receptive relaxation induced by gastric distention through both vagal nerves and capsaicin-sensitive afferent neurons. This process is intervened by endogenous NO and CGRP in addition to prostaglandins (PGs), and the effect of PGs may be mediated by EP1 receptors.
Taniguchi
M
M
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto, 607-8414, Japan.
Mashita
Y
Y
Matsuzaka
Y
Y
Kato
S
S
Takeuchi
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002208:Caproates / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D002404:Catheterization; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*; D014628:Vagotomy
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001643:Bridged Bicyclo Compounds; D002208:Caproates; D004791:Enzyme Inhibitors; C122148:ONO 8711; D010446:Peptide Fragments; D011453:Prostaglandins; C058636:calcitonin gene-related peptide (8-37); D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin