Geir O. Andersen, Mette Enger, Tor Skomedal and Jan-Bjorn Osnes
Department of Pharmacology, Faculty of Medicine, University of Oslo,
P.O. Box 1057, Blindern, N-0136 Oslo, Norway
Abstract: 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.
Keywords: alpha1-Adrenoceptor subtype, 86Rb+ efflux, Rat heart, Chloroethylclonidine,
BMY 7378