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Research ArticleArticle

EFFECTS OF INHIBITION OF MONOAMINE OXIDASE ON THE ACTIONS AND INTERACTIONS OF NOREPINEPHRINE, TYRAMINE AND OTHER DRUGS ON GUINEA-PIG LEFT ATRIUM

ROBERT F. FURCHGOTT and PEDRO SANCHEZ GARCIA
Journal of Pharmacology and Experimental Therapeutics September 1968, 163 (1) 98-122;
ROBERT F. FURCHGOTT
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PEDRO SANCHEZ GARCIA
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Abstract

Monoamine oxidase (MAO) in electrically driven left atria was inhibited by pretreatment with iproniazid or pheniprazine. Pheniprazine, while present, sensitized to norepinephrine (NE), apparently by blocking uptake. Atria from reserpine-pretreated animals have very little NE, and on incubation with NE or H3-NE, followed by a 45-min wash, showed markedly lower net uptake than did normal atria. After MAO inhibition net uptake increased in both preparations, but on a percentage basis it increased very much more in reserpine-treated atria. MAO inhibition sensitized normal atria markedly to tyramine, but only slightly to Paredrine and amphetamine; sensitization was attributed almost completely to protection of tyramine taken up by adrenergic neurons, and not of NE released. MAO inhibition produced a "secondary sensitization" to NE, characterized by a gradual, additional increase in amplitude on long exposures to NE, and a slower decline after washout. This pattern was attributed to free NE leaking from structures in which it had accumulated to levels exceeding the removal capacity of storage granules and cytoplasmic binding sites. MAO inhibition greatly enhanced the ability of exposures to NE to restore the response of reserpine-treated atria to tyramine and other indirectly acting sympathomimetics. The enhancement was due principally to protection of NE taken up. The restored response was attributed to displacement of retained NE from cytoplasmic binding sites of uptake structures (probably neurons). Tyramine (10, µg/ml, 10 min) released only part of the retained NE, but release of extremely small amounts produced very large responses. Under certain circumstances no correlation existed between retained NE and magnitude of restored response. Restored responses to cocaine appeared to be due to block of reuptake of NE leaking from uptake structures. Dopa and dopamine (MAO inhibited) and α-methyl-NE (MAO inhibited or not) were very effective in restoring response to tyramine. α-Methyl-dopa was less effective.

Footnotes

    • Received December 27, 1967.
    • Accepted March 29, 1968.
  • © 1968, by The Williams & Wilkins Company

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Journal of Pharmacology and Experimental Therapeutics
Vol. 163, Issue 1
1 Sep 1968
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Research ArticleArticle

EFFECTS OF INHIBITION OF MONOAMINE OXIDASE ON THE ACTIONS AND INTERACTIONS OF NOREPINEPHRINE, TYRAMINE AND OTHER DRUGS ON GUINEA-PIG LEFT ATRIUM

ROBERT F. FURCHGOTT and PEDRO SANCHEZ GARCIA
Journal of Pharmacology and Experimental Therapeutics September 1, 1968, 163 (1) 98-122;

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Research ArticleArticle

EFFECTS OF INHIBITION OF MONOAMINE OXIDASE ON THE ACTIONS AND INTERACTIONS OF NOREPINEPHRINE, TYRAMINE AND OTHER DRUGS ON GUINEA-PIG LEFT ATRIUM

ROBERT F. FURCHGOTT and PEDRO SANCHEZ GARCIA
Journal of Pharmacology and Experimental Therapeutics September 1, 1968, 163 (1) 98-122;
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