Summary
The influence of the alphalb-adrenoceptor-selective antagonist chlorethylclonidine on the alpha1-adrenergic positive inotropic effect and the phosphoinositide hydrolysis induced by phenylephrine was investigated in the rabbit ventricular myocardium. Pretreatment of membrane fractions derived from the rabbit ventricular muscle with 10−5 mol/l chlorethylclonidine decreased the specific binding of [3H]prazosin (at a saturating concentration of 10−9 mol/l) from the control value of 11.27±0.48 to 4.18±1.87 fmol/mg protein. The inhibition by adrenaline of the binding of [3H]prazosin (slope factor and affinity) was not affected by chlorethylclonidine. The positive inotropic effect of phenylephrine (in the presence of 3 × 10−7 mol/l bupranolol) was inhibited by chlorethylclonidine in a concentration-dependent manner (10−7−10−5 mol/l) and abolished by 10−5 mol/l chlorethylclonidine. The concentration of chlorethylclonidine to inhibit the phenylephrine-induced maximum response to 50% was 2.4 × 10−6 mol/l. The accumulation of [3H]inositol monophosphate and [3H]inositol trisphosphate induced by 10−5 mol/l phenylephrine was inhibited by chlorethylclonidine in the same concentration range. These findings indicate that the myocardial alpha1-adrenoceptors mediating a positive inotropic effect in the rabbit ventricular myocardium may belong to the chlorethylclonidine-sensitive alpha1b-subtype, and that the subcellular mechanism of action involve phosphoinositide hydrolysis.
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Takanashi, M., Norota, I. & Endoh, M. Potent inhibitory action of chlorethylclonidine on the positive inotropic effect and phosphoinositide hydrolysis mediated via myocardial alpha1-adrenoceptors in the rabbit ventricular myocardium. Naunyn-Schmiedeberg's Arch Pharmacol 343, 669–673 (1991). https://doi.org/10.1007/BF00184301
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DOI: https://doi.org/10.1007/BF00184301