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Research ArticleArticle

DISSOCIATION OF ALPHA ADRENERGIC RECEPTOR PROTECTION FROM INHIBITION OF 3H-PHENOXYBENZAMINE BINDING IN VASCULAR TISSUE

MAN SEN YONG and MARK NICKERSON
Journal of Pharmacology and Experimental Therapeutics July 1973, 186 (1) 100-108;
MAN SEN YONG
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MARK NICKERSON
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Abstract

3H-phenoxybenzamine (3H-POB) of high specific activity was synthesized, and its alpha adrenergic blocking action and tissue binding were studied in parallel on strips of rabbit thoracie aorta. The presence of a sympathomimetic amine could decrease both the blocking action and the bound radioactivity, but the two effects were not parallel. Epinephrine and α-methylnorepinephrine most effectively protected the receptors but decreased binding no more than did norepinephrine or isoproterenol. Only catecholamines (all of six tested) reduced binding significantly. Dopamine and α-methyldopamine decreased binding in the absence of significant receptor protection. Conversely, alpha and beta. adrenergic blocking agents markedly decreased the POB block without a decrease in bound radioactivity. Inhibition of both monoamine oxidase and catechol-O-methyltransferase affected binding more than blockade, perhaps due to a localized accumulation of catecholamine. It is concluded that apha adrenergic receptors represent too small a fraction of total bound POB for their protection to be detected as a decrease in binding, even with 3H-POB of high specific activity. The major decrease in binding appeared to involve "silent receptors" that are quite specific for catecholamines. This site could not be equated with any of those now known to be involved in catecholamine action or inactivation. However, it is of sufficient capacity, up to 45% of the total 3H-POB bound in the present experiments, to have an important effect on catecholamine action.

Footnotes

    • Received July 17, 1972.
    • Accepted February 26, 1973.
  • © 1972 by The Williams & Wilkins Co.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 186, Issue 1
1 Jul 1973
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Research ArticleArticle

DISSOCIATION OF ALPHA ADRENERGIC RECEPTOR PROTECTION FROM INHIBITION OF 3H-PHENOXYBENZAMINE BINDING IN VASCULAR TISSUE

MAN SEN YONG and MARK NICKERSON
Journal of Pharmacology and Experimental Therapeutics July 1, 1973, 186 (1) 100-108;

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Research ArticleArticle

DISSOCIATION OF ALPHA ADRENERGIC RECEPTOR PROTECTION FROM INHIBITION OF 3H-PHENOXYBENZAMINE BINDING IN VASCULAR TISSUE

MAN SEN YONG and MARK NICKERSON
Journal of Pharmacology and Experimental Therapeutics July 1, 1973, 186 (1) 100-108;
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