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Abstract

Kinetic characterization of the rabbit aorta contractile response to an alpha adrenergic agonist.

R N Cory, R Osman and S Maayani
Journal of Pharmacology and Experimental Therapeutics July 1984, 230 (1) 162-170;
R N Cory
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R Osman
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S Maayani
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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 [Ca++]. The kinetics of each response was characterized with respect to its dependence on [PE] and [Ca++]. The phasic response is independent of extracellular calcium and has a rapid onset followed by a first order decay. Although its maximal attainable response is saturable with respect to [PE] and [Ca++], its rate constant for onset does not depend on the concentration of calcium in the preincubation buffer. We were unable to show that this rate constant for onset is saturable with respect to [PE]. This suggests that the rate-determining step of the phasic response is the diffusion-controlled formation of the drug-receptor complex. The tonic response depends on extracellular calcium, shows first order kinetics of onset and reaches a steady-state level of contraction that is saturable with respect to [PE] and extracellular [Ca++]. The rate constant for the generation of the tonic response depends on [PE] in a saturable manner and linearly on extracellular [Ca++]. This suggests that 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 calcium ions 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.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 230, Issue 1
1 Jul 1984
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Abstract

Kinetic characterization of the rabbit aorta contractile response to an alpha adrenergic agonist.

R N Cory, R Osman and S Maayani
Journal of Pharmacology and Experimental Therapeutics July 1, 1984, 230 (1) 162-170;

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Abstract

Kinetic characterization of the rabbit aorta contractile response to an alpha adrenergic agonist.

R N Cory, R Osman and S Maayani
Journal of Pharmacology and Experimental Therapeutics July 1, 1984, 230 (1) 162-170;
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