KINETIC CHARACTERIZATION OF THE RABBIT AORTA CONTRACTILE RESPONSE TO AN ALPHA-ADRENERGIC AGONIST

  • 1 January 1984
    • journal article
    • research article
    • Vol. 230  (1) , 162-170
Abstract
The .alpha.1 adrenergic response of the rabbit aorta to phenylephrine (PE) was separated into a phasic and a tonic response by virtue of their different dependence on extracellular [Ca2+]. The kinetics of each response was characterized with respect to its dependence on [PE] and [Ca2+]. The phasic response is independent of extracellular Ca and has a rapid onset followed by a first order decay. Although its maximal attainable response is saturable with respect to [PE] and [Ca2+], its rate constant for onset does not depend on the concentration of Ca in the preinbucation buffer. That this rate constant for onset is saturable with respect to [PE] was unable to be shown. The rate-determining step of the phasic response is apparently the diffusion-controlled formation of the drug-receptor complex. The tonic response depends on extracellular Ca, shows first order kinetics of onset and reaches a steady state level of contraction that is saturable with respect to [PE] and extracellular [Ca2+]. The rate constant for the generation of the tonic response depends on [PE] in a saturable manner and linearly on extracellular [Ca2+]. The rate determining step could be the activation of a hypothetical effector by the drug-receptor complex. The activated effector would enable the transport of Ca2+ into the cell. The kinetic studies predict that the efficacy of a drug in this system is the maximal rate of activation of the effector by the drug-receptor complex.