Carteolol, a non-conventional partial agonist of beta(1)-adrenoceptors, relaxes phenylephrine-constricted rat aorta through antagonism at alpha(1)-adrenoceptors. European journal of pharmacology [Eur J Pharmacol] Journal article | | Title | Carteolol, a non-conventional partial agonist of beta(1)-adrenoceptors, relaxes phenylephrine-constricted rat aorta through antagonism at alpha(1)-adrenoceptors. | | Author(s) | Floreani M, Quintieri L, Varani K, Dorigo MT, Dorigo P | | Institution | Department of Pharmacology and Anaesthesiology, University of Padova, Italy. | | Source | Eur J Pharmacol 2008 May 24. | | Abstract | This in vitro study was designed to investigate whether carteolol, a non-conventional partial agonists of beta(1)-adrenoceptors, relaxes phenylephrine-constricted rat aorta through activation of the low-affinity state of beta(1)-adrenoceptors or antagonist effect at alpha(1)-adrenoceptors. Carteolol-induced complete concentration-dependent relaxation of phenylephrine-contracted aorta (pD(2)=3.65+/-0.04), this effect not being modified by endothelium removal and not antagonised by NO-synthase inhibitor N(G)-nitro-l-arginine methyl ester (100 microM) or cyclo-oxygenase inhibitor indomethacin (10 microM). The effect of carteolol was unaffected by the non-selective beta-adrenoceptor antagonist propranolol (1 microM), or the beta(2)-adrenoceptor selective antagonist (+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol (ICI 118,551, 1 microM). Increasing concentrations of carteolol produced a parallel rightward shift of the concentration-response curves for phenylephrine-induced contraction, exhibiting a pK(B) of 4.28+/-0.07. Carteolol affinity for alpha(1)-adrenoceptors was evaluated by means of competition experiments carried out in BHK-21 cell membranes expressing rat recombinant alpha(1D)-adrenoceptor, the alpha(1)-adrenoceptor subtype mainly present in rat aorta. Carteolol competed monophasically with [(3)H]prazosin, exhibiting a pK(i) value (3.39+/-0.31) similar to its pD(2) and not very far from its pK(B). In conclusion, this study indicates that carteolol relaxes phenylephrine-contracted aorta through its alpha(1)-adrenoceptor antagonist properties, excluding the possibility that the relaxant effect is due to the activation of beta-adrenoceptors, particularly of the low-affinity state of beta(1)-adrenoceptors, by the drug. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 18571646 |
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