1. We have previously shown (Malinowska & Schlicker, 1996) that the atypical beta-
adrenoceptor involved in the positive chronotropic effect of the so-called non-conventional partial beta-
adrenoceptor agonists
CGP 12177 and
cyanopindolol in the pithed rat possesses properties markedly different from those observed for beta3-adrenoceptors in the literature. In the present study, we have directly compared the pharmacological properties of the atypical cardiostimulant beta-
adrenoceptor and of the beta3-adrenoceptor mediating the thermogenic response in the brown adipose tissue in pithed and vagotomized rats. 2. Heart rate was dose-dependently increased by
CGP 12177 and
cyanopindolol by maximally 150 and 100 beats min(-1), yielding pED50 values of 8.0 and 7.3, respectively (pED50, -log10 of the dose in mol kg(-1)
body weight i.v. causing the half-maximum effect), but not affected by the selective beta3-adrenoceptor agonist
CL 316243 (pED50 > 6.0). 3.
CGP 12177,
cyanopindolol and
CL 316243 increased temperature in the brown adipose tissue by maximally 1 degree C (pED50 values 7.4, 6.3 and 8.6, respectively). 4. The beta1-adrenoceptor antagonist
CGP 20712 10 micromol kg(-1), attenuated the cardiostimulatory effect of
CGP 12177 and, at a still higher dose (30 micromol kg(-1)), also antagonized its thermogenic effect. The -log10 values of the doses causing a two fold shift of the dose-response curves (DRCs) of
CGP 12177 to the right were 6.1 and 5.2, respectively, and were much lower than the corresponding value for the antagonism of
CGP 20712 against the beta1-adrenoceptor-mediated positive chronotropic effect which was 8.6. 5. The cardiostimulant and the thermogenic effect of
CGP 12177 were not affected by the beta2-adrenoceptor antagonist
ICI 118551 10 micromol kg(-1). 6. The beta3-adrenoceptor antagonist
SR 59230A (which, by itself, caused a beta1-
adrenoceptor-mediated increase in heart rate and, for this reason, was studied after administration of a low dose of
CGP 20712) attenuated the cardiostimulant and the thermogenic effect of
CGP 12177 to a similar extent. The -log10 values of the doses causing two fold rightward shifts of the DRCs of
CGP 12177 were 5.9 and 5.7, respectively. 7. The non-selective
beta-adrenoceptor antagonist bupranolol diminished the cardiostimulant and thermogenic response to a very similar extent. The -log10 values causing two fold rightward shifts of the DRCs of
CGP 12177 were 5.6 and 5.7, respectively, and were much lower than the corresponding values for the antagonism of
bupranolol against the beta1-adrenoceptor-mediated positive chronotropic effect and the beta2-adrenoceptor-mediated decrease in diastolic blood pressure which were 7.6 and 8.3, respectively. 8. The rank order of agonistic potencies for the cardiostimulant effect (
CGP 12177 >
cyanopindolol >
CL 316243) differs from that for the thermogenic response in the brown adipose tissue (
CL 316243 >
CGP 12177 >
cyanopindolol); furthermore, there is a difference with respect to the rank orders of antagonistic potencies for cardiostimulation (
CGP 20712 > or =
SR 59230A > or =
bupranolol >
ICI 118551) and thermogenesis (
SR 59230A =
bupranolol >
CGP 20712 >
ICI 118551). 9. In conclusion, our study provides further evidence that the atypical cardiostimulant beta-
adrenoceptors (causing an increase in heart rate) and beta3-adrenoceptors are pharmacologically different.