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Journal of Pharmacology And Experimental Therapeutics, Vol. 184, Issue 2, 346-356, 1973
Copyright © 1973 by American Society for Pharmacology and Experimental Therapeutics

INHIBITION OF ADRENERGIC NEUROTRANSMISSION BY PARASYMPATHOMIMETICS IN THE RABBIT EAR ARTERY

ODD S. STEINSLAND 1, ROBERT F. FURCHGOTT 1, and S. M. KIRPEKAR 1

1 Department of Pharmacology, State University of New York, Downstate Medical Center, Brooklyn, New York

The isolated central ear artery of the rabbit was perfused at a constant flow rate with Krebs' solution and perfusion pressure was recorded with a transducer. Acetylchohine (ACh) in concentrations from 0.001 to 1.0. µg/ml produced a dose-dependent inhibition of the vasoconstrictor response to field stimulation of the periarterial nerves but did not inhibit the vasoconstrictor response to exogenous norepinephrine. Nerve-evoked vasoconstriction also was inhibited by carbachol, methacholine aud pilocarpine. Pilocarpine acted as a partial agonist. ACh was about 4 times as potent as carbachol before inhibition of cholinesterase and about 8 times as potent after inhibition with physostigmine or diisopropyl phosphorofluoridate. Atropine antagonized the inhibitory effects of these parasympathomimetics in a competitive manner. The calculated dissociation constant (KB) of the atropine-receptor complex was 8.0 ± 0.9 x 10-10 M. ACh inhibited the nerveevoked release of radioactivity from arteries preperfused with 3H-norepinephrine. We have concluded that ACh and the other Parasympathomimetics, acting on neuronal muscarinic receptors at or near the adrenergic nerve terminals, interfere with the process by which nerve stimulation causes release of norepinephrine and thus inhibit nerveevoked vasoconstriction.

Submitted on July 24, 1972
Accepted on October 19, 1972




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O. Steinsland and J. Hieble
Dopaminergic inhibition of adrenergic neurotransmission as a model for studies on dopamine receptor mechanisms
Science, January 27, 1978; 199(4327): 443 - 445.
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Copyright © 1973 by the American Society for Pharmacology and Experimental Therapeutics.