Concentration-response relationship of alpha 1-adrenoceptor-stimulated increase of 86Rb+ efflux in rat heart.
The aim of the present study was to establish a concentration-response relationship for the alpha 1-adrenoceptor mediated increase of 86Rb+ efflux, and to characterize the sensitivity of this response to the selective alpha 1-adrenoceptor antagonist prazosin. Isolated rat hearts were perfused retrogradely at constant flow and at 31 degrees. Timolol (10(-6) mol/l) was used to block beta-adrenoceptors. After a loading period with 86Rb+ and 55 min. washout, the hearts were exposed to phenylephrine in a concentration range from 3 x 10(-8) mol/l to 10(-4) mol/l. Control experiments comparing the effects of alpha 1-adrenoceptor stimulation on 86Rb+ efflux and 42K+ efflux were performed. alpha 1-Adrenoceptor stimulation increased the 86Rb+ efflux with a pD2 = 6.35 +/- 0.20 (mean +/- S.E.M). The maximal response to phenylephrine was 22.5 +/- 2.0% (mean +/- S.E.M.) of the control values. The concentration-response curve was shifted to higher concentration of agonist in the presence of the alpha 1-adrenoceptor antagonist prazosin (3 x 10(10) mol/l). The calculated inhibition constant for prazosin was 6.1 x 10(-11) mol/l. 86Rb+ was found to be a suitable K+ analogue in the study of relative changes in K+ efflux although the basal efflux kinetics were different for the two isotopes.


CONCLUSIONS
Phenylephrine increased the 86+b+ efflux concentration-dependently. A high sensitivity to prazosin confirmed the involvement of the alpha 1-adrenoceptor population.
Department of Pharmacology, University of Oslo, Norway.
G O
GO
Andersen
M
M
Enger
T
T
Skomedal
J B
JB
Osnes
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects*; D007553:Isotope Labeling; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012413:Rubidium / Q000378:metabolism*; D013999:Timolol / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D010656:Phenylephrine; D013999:Timolol; D012413:Rubidium; D011188:Potassium; D011224:Prazosin