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Abstract

Studies on vascular dopamine receptors with the dopamine receptor agonist: SK&F 82526.

E H Ohlstein, B Zabko-Potapovich and B A Berkowitz
Journal of Pharmacology and Experimental Therapeutics May 1984, 229 (2) 433-439;
E H Ohlstein
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B Zabko-Potapovich
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B A Berkowitz
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Abstract

The vascular effects of a new dopamine receptor agonist, SK&F 82526, were evaluated in isolated rabbit splenic arterial ring segments. In this preparation, previously shown to possess dopamine receptors, SK&F 82526 produced a stereoselective relaxation with the R-enantiomer more active (ED50 1 X 10(-6) M) than the S-enantiomer (ED50 7 X 10(-6) M). Because SK&F 82526 lacks alpha agonist adrenoreceptor activity, a unique feature of these studies was the ability to examine the relaxant action of a dopamine receptor agonist using norepinephrine to contract the tissue in the absence of phenoxybenzamine which is required to antagonize the alpha adrenoreceptor agonist activity of other dopamine receptor agonists. Dopamine receptor antagonists inhibited SK&F 82526-mediated vascular relaxation with the following pA2 values: metoclopramide, 5.20; R-sulpiride, 4.96; and bulbocapnine, 4.62. Initial studies on the location of the receptors, and possible biochemical mechanisms, involved in the relaxation were undertaken. The relaxant effect of SK&F 82526 was decreased when the vascular endothelium was removed. However, removal of the endothelium did not produce a generalized inability to inhibit vascular relaxation because nitroglycerin relaxation of this tissue was not reduced. Phosphodiesterase inhibitors potentiated the vascular relaxant effects of SK&F 82526 only when the endothelium was present. This evidence suggests that a cyclic nucleotide-mediated process may be involved. In summary, direct physiologic evidence for the vascular relaxant effects of SK&F 82526 being mediated on postjunctional dopamine receptors is presented. This drug is a useful agent for the study and characterization of dopamine receptors.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 229, Issue 2
1 May 1984
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Abstract

Studies on vascular dopamine receptors with the dopamine receptor agonist: SK&F 82526.

E H Ohlstein, B Zabko-Potapovich and B A Berkowitz
Journal of Pharmacology and Experimental Therapeutics May 1, 1984, 229 (2) 433-439;

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Abstract

Studies on vascular dopamine receptors with the dopamine receptor agonist: SK&F 82526.

E H Ohlstein, B Zabko-Potapovich and B A Berkowitz
Journal of Pharmacology and Experimental Therapeutics May 1, 1984, 229 (2) 433-439;
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