caa a22 4500 469079738 CHVBK 20180323132946.0 cr unu---uuuuu 170328e19920501xx s 000 0 eng 10.1007/BF00168952 doi (NATIONALLICENCE)springer-10.1007/BF00168952 Role of alpha1A adrenoceptor subtype in production of the positive inotropic effect mediated via myocardial alpha, adrenoceptors in the rabbit papillary muscle: influence of selective alpha1A subtype antagonists WB 4101 and 5-methylurapidil [Elektronische Daten] [M. Endoh, M. Takanashi, I. Norota] Summary: In order to elucidate the contribution of alpha1A subtype to the positive inotropic effect mediated by myocardial alpha, adrenoceptors, the influence of the alpha1A selective antagonists WB 4101 and 5-methylurapidil on the alpha,-mediated positive inotropic effect (induced by phenylephrine in the presence of a beta adrenoceptor blocking agent bupranolol) was assessed in the isolated rabbit papillary muscle. WB 4101 (10−9-10−7mol/l) shifted the concentration-response curve of the alpha,-mediated positive inotropic effect to the right in parallel, but the slope of Schild plot did not meet the competitive antagonism: WB 4101 shifted the curve by log one unit at 10−9 mol/1, whereas it did not cause further shift at higher concentrations of 10−8 and 10−7 mol/l. WB 4101 did not affect the beta adrenoceptor-mediated positive inotropic effect. 5-Methylurapidil (10−9 to 10−7 mol/l) shifted the curve of alpha1-mediated positive inotropic effect to the right and downwards in a concentration-dependent manner; the slope of Schild plot calculated at the level of 20% of the maximum response to phenylephrine was close to unity. 5-Methylurapidil at 3 × 10−7 mol/1 abolished the alpha1-mediated positive inotropic effect. In addition, 5-methylurapidil inhibited the beta adrenoceptor-mediated positive inotropic effect in the same concentration range as it antagonized the alpha1-mediated positive inotropic effect, indicating that 5-methylurapidil is not selective for myocardial alpha, adrenoceptors. In the membrane fraction derived from the rabbit ventricular muscle, 5-methylurapidil displaced the specific binding of [3H]CGP-12177 with high affinity, whereas WB 4101 did not affect the [3H]CGP-12177 binding in the concentration range that it antagonized the alpha,-mediated positive inotropic effect. The present results indicate that alpha1A adrenoceptor subtype plays a role in production of the positive inotropic effect mediated by myocardial alpha, adrenoceptors, but the extent is less than that mediated by alpha1B subtype in the rabbit ventricular myocardium. Springer-Verlag, 1992 WB 4101 nationallicence 5-Methylurapidil nationallicence Alpha1 adrenoceptors nationallicence Positive inotropic effect nationallicence [3H]CGP-12177 nationallicence Rabbit papillary muscle nationallicence Endoh M. Department of Pharmacology, Yamagata University School of Medicine, 990-23, Yamagata, Japan aut Takanashi M. Department of Pharmacology, Yamagata University School of Medicine, 990-23, Yamagata, Japan aut Norota I. Department of Pharmacology, Yamagata University School of Medicine, 990-23, Yamagata, Japan aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/5(1992-05-01), 578-585 0028-1298 345:5<578 1992 345 210 https://doi.org/10.1007/BF00168952 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00168952 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Endoh M. Department of Pharmacology, Yamagata University School of Medicine, 990-23, Yamagata, Japan aut NATIONALLICENCE 700 1- Takanashi M. Department of Pharmacology, Yamagata University School of Medicine, 990-23, Yamagata, Japan aut NATIONALLICENCE 700 1- Norota I. Department of Pharmacology, Yamagata University School of Medicine, 990-23, Yamagata, Japan aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/5(1992-05-01), 578-585 0028-1298 345:5<578 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer