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Am J Physiol Gastrointest Liver Physiol 272: G1000-G1006, 1997;
0193-1857/97 $5.00
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AJP - Gastrointestinal and Liver Physiology, Vol 272, Issue 5 1000-G1006, Copyright © 1997 by American Physiological Society

ARTICLES

Characterization of a beta 3-adrenoceptor stimulating gastrin and somatostatin secretions in rat antrum

S. Levasseur, A. Bado, J. P. Laigneau, L. Moizo, F. Reyl-Desmars and M. J. Lewin
Institut National de la Sante et de la Recherche Medicale Unite 10, Paris, France.

The beta 3-adrenoceptor (beta 3-AR) agonist SR-58611A inverted question markethyl-[(7s)-7-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]5, 6,7,8-tetrahydronaphth-2-yl]oxyacetate hydrochloride inverted question mark stimulated somatostatin and gastrin releases in isolated rat gastric antral epithelial cells. Stimulation was a concentration-dependent process with 50% effective concentrations of 2.7 +/- 1.1 and 3.8 +/- 1.9 nM compared with 209 +/- 71 and 230 +/- 51 nM for isoproterenol, respectively. It was inhibited by selective beta-AR antagonists with the following rank order of potency: SR-59230A 3-(2-ethylphenoxy)1-[(1S)-1,2,3,4-tetrahydronaphth- 1-ylamino]-(2S)-2-propranol oxalate; beta 3-AR antagonist > ICI-118551[erythro-(+/-)-1-(7-methylindan-4-yloxy)-3- isopropylaminobutan-2-ol-hydrochloride; beta 2-AR antagonist > CGP-20712A[(+/-)-[2-(3-carbarmoyl-4-hydroxyphenoxy)-et hyl- amino]-3-[4 (1-methyl-4-trifluoromethyl-2-imidazolyl)-phenoxy]- 2-propranol; beta 1-AR antagonist]. Furthermore, specific binding of 125I-cyanopindolol to the isolated cells was demonstrated and was displaced by the beta-AR antagonists according to the same rank order of potency and with apparent dissociation constants consistent with the 50% inhibitory concentrations for SR-58611A-stimulated somatostatin and gastrin releases. In addition, the presence of beta 3-AR mRNA was detected by reverse transcriptase polymerase chain reaction. These findings provide the first evidence for a gastric beta 3-AR mediating catecholamine stimulation of gastrin and somatostatin releases from antral cells.


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 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
A. B. M. Grudell, M. Camilleri, K. L. Jensen, A. E. Foxx-Orenstein, D. D. Burton, M. D. Ryks, K. L. Baxter, D. S. Cox, G. E. Dukes, D. L. Kelleher, et al.
Dose-response effect of a {beta}3-adrenergic receptor agonist, solabegron, on gastrointestinal transit, bowel function, and somatostatin levels in health
Am J Physiol Gastrointest Liver Physiol, May 1, 2008; 294(5): G1114 - G1119.
[Abstract] [Full Text] [PDF]


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