(+/-)-tamsulosin, an alpha 1A-adrenoceptor antagonist, inhibits the positive inotropic effect but not the accumulation of inositol phosphates in rabbit heart.
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Yang HT, Endoh M
(+/-)-tamsulosin, an alpha 1A-adrenoceptor antagonist, inhibits the positive inotropic effect but not the accumulation of inositol phosphates in rabbit heart.
Eur J Pharmacol. 1996 Oct 3;312(3):281-91.
- PubMed ID
- 8894610 [ View in PubMed]
- Abstract
The influence of (+/-)-tamsulosin, a selective alpha 1A-adrenoceptor antagonist, on the positive inotropic effect and the accumulation of inositol phosphates that are induced via alpha 1-adrenoceptors was studied in comparison with that of another alpha 1A-adrenoceptor ligand oxymetazoline in the rabbit ventricular myocardium. Phenylephrine elicited a concentration-dependent positive inotropic effect via alpha 1-adrenoceptors in the presence of either (+/-)-bupranolol or S(-)-timolol. The mode of antagonism induced by (+/-)-tamsulosin on the effect of phenylephrine was dependent or the concentration applied: (+/-)-tamsulosin at 1 and 3 nM acted in a competitive manner, the slope of the regression line of the Schild plot being unity and the pA2 value being 9.12; at 10 nM, it shifted further the concentration-response curve to the right without affecting the maximal response but the slope became less than unity. At 100 nM and higher, it suppressed the maximal response to phenylephrine. (+/-)-Tamsulosin effectively antagonized the positive inotropic effect of phenylephrine even after inactivation of alpha 1B-adrenoceptors by treatment with chlorethylclonidine, which is an indication that the (+/-)-tamsulosin-sensitive subtype belongs to a class resistant to chlorethylclonidine. (+/-)-Tamsulosin, over the range of concentrations at which it antagonized the positive inotropic effect mediated by alpha 1-adrenoceptors, did not affect the accumulation of [3H]inositol phosphates that was induced by 10 microM phenylephrine. Oxymetazoline antagonized the positive inotropic effect of phenylephrine in a competitive manner without affecting the accumulation of inositol monophosphate induced by phenylephrine. These results indicate that the positive inotropic effect, mediated via (+/-)-tamsulosin- and oxymetazoline-sensitive subtype of alpha 1-adrenoceptors, is exerted by a subcellular mechanism that is independent of the accumulation of inositol phosphates.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Oxymetazoline Alpha-1A adrenergic receptor Protein Humans YesPartial agonistDetails Xylometazoline Alpha-1A adrenergic receptor Protein Humans YesAgonistPartial agonistDetails