Abstract
We investigated the mechanisms of neurally mediated relaxation of cat gallbladder muscle. Muscle strips from the gallbladder corpus placed in the muscle bath with oxygenated Krebs’ solution developed spontaneous active tension. Tension was measured with isometric force transducers, and muscle relaxation was expressed as percent decrease of active basal tension. Electrical field stimulation (EFS) evoked a tetrodotoxin-sensitive and hexamethonium-insensitive frequency-dependent relaxation with a maximal relaxation at 20 Hz. Gallbladder muscle strips also relaxed in response to increasing concentrations of vasoactive intestinal peptide (VIP), isoproterenol and, after pretreatment with phentolamine, norepinephrine. Nitric oxide synthase inhibitors Nω-nitro-l-arginine and Nω-nitro-l-arginine methyl ester at a concentration of 100 μM, which blocked EFS-induced relaxation in the lower esophageal sphincter, had no significant effect on EFS-induced gallbladder muscle relaxation. The VIP antagonists VIP10–28 and [4Cl-d-Phe6,Leu17]VIP at a concentration of 10 μM that blocked exogenous VIP-induced gallbladder relaxation also had no effect on the relaxation caused by EFS. In contrast, either propranolol or guanethidine at concentrations of ≥1 μM significantly reduced EFS-evoked gallbladder relaxation (P < .01, analysis of variance). It is concluded that norepinephrine utilizing beta adrenergic receptors mediates EFS-stimulating postganglionic intramural neurons in the cat gallbladder.
Footnotes
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Send reprint requests to: Jose Behar, M.D., Division of Gastroenterology, APC 421, Rhode Island Hospital and Brown University, 593 Eddy Street, Providence, RI 02903.
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↵1 This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grant R01-DK27389.
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↵2 These data were presented in part at the 9th American Motility Society Biennial Meeting, Traverse City, MI, 1996.
- Abbreviations:
- ANOVA
- analysis of variance
- EFS
- electrical field stimulation
- LES
- lower esophageal sphincter
- CCK
- cholecystokinin
- L-NA
- Nω-nitro-l-arginine
- L-NAME
- Nω-nitro-l-arginine methyl ester
- NE
- norepinephrine
- NO
- nitric oxide
- TTX
- tetrodotoxin
- VIP
- vasoactive intestinal peptide
- Received September 8, 1997.
- Accepted January 20, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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