Pharmacological evidence for alpha(1D)-adrenoceptors in the rabbit ventricular myocardium: analysis with BMY 7378

British Journal of Pharmacology
H T Yang, M Endoh

Abstract

1. It was examined by means of BMY 7378, a selective antagonist of alpha 1D-adrenoceptors, whether alpha 1D-adrenoceptors contribute to the regulation of myocardial contractility and hydrolysis of phosphoinositide (PI) in rabbit ventricular muscle. 2. BMY 7378 had a biphasic antagonistic action on the positive inotropic effect (PIE) of phenylephrine depending on the concentration. BMY 7378 at 1-10 nM shifted the concentration-response curve (CRC) for the PIE of phenylephrine to the right and downward and at 100 nM to 1 microM it antagonized the PIE in a competitive manner, the slope of Schild plot being 0.93 and the pA2 being 7.17 +/- 0.09. 3. The inhibitory action of BMY 7378 at 1-10 nM is ascribed to the selective action on alpha 1-adrenoceptors because the PIE of neither isoprenaline nor endothelin-3 and angiotensin II was affected by this compound over this concentration range. 4. In the presence of 100 nM WB 4101, the antagonistic action of BMY 7378 at 1-10 nM remained unchanged but the antagonistic action of BMY 7378 at 100-300 nM disappeared. The antagonistic action of BMY 7378 at 1 nM was unaffected by 100 nM (+)-niguldipine. 5. Following pretreatment with chloroethyldonidine, BMY 7378 at 1 nM inhibited the maximal resp...Continue Reading

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Citations

Jan 15, 2008·Naunyn-Schmiedeberg's Archives of Pharmacology·Diana Marcela Rojas GomezStefan Dhein
Oct 29, 2009·Cellular and Molecular Life Sciences : CMLS·James R Docherty
Jun 27, 2006·Journal of Pharmacological Sciences·Masao Endoh
Jan 24, 2002·Biology of Reproduction·Daniel B C QueirózMaria Christina W Avellar
Sep 20, 2000·American Journal of Physiology. Heart and Circulatory Physiology·B H WangE A Woodcock
Jul 27, 2001·Archives of Biochemistry and Biophysics·S SeraskerisA Lazou
Sep 1, 2001·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·B Civantos Calzada, A Aleixandre de Artiñano
Dec 16, 1998·European Journal of Pharmacology·J R Docherty

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