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Journal of Pharmacology And Experimental Therapeutics, Vol. 180, Issue 3, 636-646, 1972
Copyright © 1972 by American Society for Pharmacology and Experimental Therapeutics

A RECEPTOR KINETIC MODEL OF A VASCULAR NEUROEFFECTOR

BÖRJE JOHANSSON 1, STEN R. JOHANSSON 1, BENGT LJUNG 1, and LARS STAGE 1

1 Department of Physiology, University of Göteborg and Department of Physiology, University of Lund, Sweden

The alpha adrenergic control of a propagating vascular smooth muscle, the isolated portal vein of the rat, was analyzed. The purpose of the study was to investigate whether a single model of the receptor-agonist reaction would quantitatively account for responses both to nerve stimulation and to exogenous norepinephrine (NE). The dissociation constant of the receptor-agonist complex was found to be 1.26 x 10-6 M. Receptor kinetics and an expression relating fractional receptor occupancy to response gave a theoretical dose-response curve for exogenous NE which was consistent with the experimental resuits. Transmitter concentrations at the receptors, 1000 å from the sites of neural release, were calculated by applying the diffusion equation and were found to be characterized by peaks exceeding 10-5 M. Theoretical frequency-response curves could be calculated by considering the qualitative properties of these transmitter peaks and the agonist receptor relation developed for exogenous NE. Consistency between theoretical and experimental frequency-response curves was obtained under conditions where the NE peaks caused high levels of initial receptor occupancy. This suggests that a single receptor-agonist reaction can determine alpha adrenergic responses of this neuroeffector both to exogenous NE and to nerve stimulation despite the obvious difference in the distribution of the agonist.

Submitted on March 30, 1971
Accepted on November 29, 1971




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Copyright © 1972 by the American Society for Pharmacology and Experimental Therapeutics.