Open AccessReceptor Subtypes Involved in the .ALPHA.1-Adrenoceptor Mediated Increase in 86Rb+ Efflux from the Rat Heart.
Author(s) -
Geir Øystein Andersen,
Mette Enger,
Tor Skomedal,
JanBjørn Osnes
Publication year - 1997
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.75.171
Subject(s) - phenylephrine , efflux , adrenergic receptor , medicine , endocrinology , chemistry , stimulation , antagonist , alpha (finance) , agonist , pharmacology , receptor , biology , biochemistry , construct validity , nursing , blood pressure , patient satisfaction
The aim of this study was to determine the involvement of the different alpha1-adrenoceptor subtypes in the alpha1-adrenoceptor mediated increase in 86Rb+ efflux from rat hearts. Isolated hearts were perfused in the presence of a beta-adrenoceptor antagonist (1 microM timolol). After loading with 86Rb+, the efflux was measured during alpha1-adrenoceptor stimulation by phenylephrine (30 microM). Phenylephrine increased the 86Rb+ efflux by about 30%. Pretreatment with the preferentially alpha1B-adrenoceptor inhibitor chloroethylclonidine (CEC), reduced the response to phenylephrine by about 50%. The preferential alpha1D-adrenoceptor inhibitor BMY 7378 inhibited the response to phenylephrine by 35%, with a pKI=8.4 (95% C.I. 8.2-8.6). The response was sensitive to the preferential alpha1A-adrenoceptor inhibitors (+)niguldipine, 5-methylurapidil (5-MU) and WB-4101 at relatively high concentrations, and 5-MU inhibited the response with a pKI=7.7 (95% C.I. 7.2-8.0) in CEC pretreated hearts. In conclusion, the phenylephrine stimulated increase in 86Rb+ efflux in the rat heart is not specifically linked to only one of the alpha1-adrenoceptor subtypes, but involves the alpha1B- and the alpha1D-adrenoceptor subtypes, and probably the alpha1A-adrenoceptor subtype as well.