Pharmacological study of atypical β-adrenoceptors in rat esophageal smooth muscle
| Autor: | Dennis R. Feller, M. Margarita Salazar‐Bookaman, Anish A. Konkar, Duane D. Miller, Edwin J. Lezama |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Agonist medicine.medical_specialty medicine.drug_class Muscle Relaxation Adrenergic beta-Antagonists Cyclohexane Monoterpenes In Vitro Techniques Phenoxyacetates Medicinal chemistry Partial agonist Phenoxypropanolamines Propanolamines Rats Sprague-Dawley chemistry.chemical_compound Esophagus Pindobind Adrenergic beta-2 Receptor Antagonists Internal medicine Phenethylamines Receptors Adrenergic beta medicine Animals Clenbuterol Heart Atria Pindolol Pharmacology Isoproterenol Muscle Smooth Adrenergic beta-1 Receptor Antagonists Rats Trachea Schild regression Ractopamine Endocrinology chemistry Ethanolamines Carbachol Female Tretoquinol Stereoselectivity Serotonin Antagonists medicine.drug |
| Zdroj: | European Journal of Pharmacology. 308:69-80 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/0014-2999(96)00236-1 |
| Popis: | The chemical specificity for the beta-adrenoceptor mediated relaxation of rat esophageal smooth muscle was evaluated using selective and non-selective beta-adrenoceptor agonists and antagonists. Pindolol, ICI 89,406, ICI 118551 [erythro-1-(7-methylindan-4-yloxy)-3-(isopropylamine)-but an-2-ol] and the beta-adrenoceptor alkylating agent, pindobind, produced only small rightward shifts in the concentration-response curves of (-)-isoprenaline and (-)-trimetoquinol in this preparation. Rank order potency (pD2 values) of agonists was: (+/-)-trimetoquinol [1-(3',4',5'-trimethoxybenzyl)-6,7-dihydroxy-1,2,3, 4-tetrahydroisoquinoline] (8.34) = (-)-trimetoquinol (8.26) = BRL 37344 [(R* R*)-(+/-)-4-[2'-2-hydroxy 2-(3-chlorophenyl)ethylamino]propyl] phenoxyacetic acid] (8.16) = ICID7114 [(S)-4-(2-hydroxy- 3-phenoxy-propylamino-ethoxy)-N-(2-methoxyethyl) phenoxyacetamide] (8.03)or = (-)-isoprenaline (7.82)3',5'-diiodotrimetoquinol [1-(3',5'-diiodo-4'-methoxybenzyl)-6, 7-dihydroxy-1,2,3,4-tetrahydroisoquinoline] (7.28)3'-iodotrimetoquinol [1-(3'-iodo-4',5'-dimethoxybenzyl)-6, 7-dihydroxy-1,2,3,4-tetrahydroisoquinoline] (7.04)ractopamine (6.84) = 5,8-difluorotrimetoquinol [5,8-difluoro-6,7-dihydroxy-1- (3',4',5'-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline] (6.82)8-fluorotrimetoquinol [6,7-dihydroxy-8-fluoro-1-(3',4',5'- trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline] (6.56)or = (-)-noradrenaline (6.46)or = (-)-adrenaline (6.36)(+/-)-noradrenaline (6.24)(+/-)-adrenaline (6.00)clenbuterol (5.83)(-)-1-benzyl-6, 7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (5.75). Isomeric activity ratios of trimetoquinol isomers [(-)-(S)-(+)-(R)-] in esophageal smooth muscle in the presence and absence of 1 microM pindolol were 1995- and 2951-fold, respectively; and were much greater than those in rat atria (282-fold) and rat trachea (107-fold). The atypical beta/beta 3-adrenoceptor partial agonist, ICI D7114, produced concentration-dependent rightward shifts of the concentration-response curves of (-)-isoprenaline, (-)-trimetoquinol and the reference atypical beta/beta 3-adrenoceptor agonist, BRL 37344. Schild plot analysis of ICI D7114 against trimetoquinol gave slope and pA2 values of 0.91 and of 7.9, respectively. These results clearly demonstrate that the relaxant effects of these agonists in rat esophageal smooth muscle are primarily mediated through the activation of atypical beta/beta 3-adrenoceptors. (-)-Trimetoquinol was as potent as (-)- isoprenaline and BRL 37344, and was the most stereoselective agonist evaluated in this tissue system. |
| Databáze: | OpenAIRE |
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