TY - JOUR T1 - A RECEPTOR KINETIC MODEL OF A VASCULAR NEUROEFFECTOR JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 636 LP - 646 VL - 180 IS - 3 AU - BÖRJE JOHANSSON AU - STEN R. JOHANSSON AU - BENGT LJUNG AU - LARS STAGE Y1 - 1972/03/01 UR - http://jpet.aspetjournals.org/content/180/3/636.abstract N2 - 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. © 1972 by The Williams & Wilkins Co. ER -