DETERMINATION OF THE STIMULUS-RESPONSE RELATION FOR 3 ALPHA-ADRENERGIC AGONISTS ON RABBIT AORTA

  • 1 January 1979
    • journal article
    • research article
    • Vol. 241  (2) , 197-207
Abstract
A standard rabbit thoracic-aorta strip preparation was used to determine the effect of varying preload on KA (the dissociation constant), A50(the concentration that produces half maximal response) and the ratio KA/A50. The stimulus-response relationships were obtained for the drug and preload conditions tested. Values of KA and A50 were calculated from dose-response curves obtained for 3 .alpha.-adrenergic agonists (phenylephrine, methoxamine and norepinephrine) in the presence and absence of partial irreversible blockade by phenoxybenzamine. For all 3 drugs, values of KA and A50 were significantly greater at 1/4 g preload than at 10 g preload. The ratio KA/A50 was independent of preload conditions. The stimulus-response relationships were non-linear, in contrast to the predictions of classical receptor theory. The significance of the constancy of KA/A50, rather than KA or A50, and the non-linear relation between drug stimulus and response are discussed in terms of Stephenson''s theory of drug action.

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