A beta adrenoceptor with atypical characteristics is involved in the relaxation of the rat small intestine.
In several studies in guinea pig ileum or rat colon a beta adrenoceptor with characteristics distinct from beta-1 or beta-2 receptors has been observed and has been denoted as "atypical" beta adrenoceptor. In this study the relaxation of the rat small intestine was investigated, using isolated segments of the rat jejunum. Several beta-1 or beta-2 agonists and antagonists were tested on the rat jejunum preparation, and it was found that nonselective and selective antagonists for beta-1 or beta-2 receptors showed a relatively low affinity, compared to their affinity for beta-1 or beta-2 receptors. BRL 37344, an agonist which has been reported to be selective for the atypical beta adrenoceptor, was more potent although a partial agonist compared to isoprenaline, whereas it is clearly less active than isoprenaline on beta-1 or beta-2 receptors. These findings indicate that beta adrenergic relaxation of the rat small intestine is mediated via atypical beta adrenoceptors. Efforts were made to confirm these findings with binding studies on small intestinal 45,000-g membranes. Competition radioligand binding experiments were performed with the radiolabeled ligand [125I]iodocyanopindolol and the various antagonists which were also tested in the intact rat jejunum preparations. Receptor binding experiments only revealed beta adrenoceptors of the beta-2-subtype, which does not correspond with the results obtained in the jejunum relaxation. Probably the beta-2 receptors found in the binding studies are located on circular smooth muscle cells or on epithelial cells, whereas longitudinal smooth relaxation is mediated by atypical beta adrenoceptors. Atypical beta adrenoceptors were not measured in binding studies probably because [125I]iodocyanopindolol is an unsuitable ligand to label atypical intestinal beta adrenoceptors.
van der Vliet
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A
Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universteit, Amsterdam, The Netherlands.
Rademaker
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B
Bast
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D000273:Adipose Tissue / Q000737:chemistry; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004983:Ethanolamines / Q000494:pharmacology; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects / Q000502:physiology*; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; C057368:BRL 37344; D020120:Iodocyanopindolol; D010869:Pindolol; D007545:Isoproterenol; D009638:Norepinephrine; D011224:Prazosin