KINETIC CHARACTERIZATION OF THE CONTRACTILE RESPONSE OF THE RABBIT AORTA TO ALPHA-1 ADRENERGIC AND SEROTONERGIC AGONISTS (PHARMACOLOGY, DRUG, RECEPTORS, EFFICACY).
Item
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Title
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KINETIC CHARACTERIZATION OF THE CONTRACTILE RESPONSE OF THE RABBIT AORTA TO ALPHA-1 ADRENERGIC AND SEROTONERGIC AGONISTS (PHARMACOLOGY, DRUG, RECEPTORS, EFFICACY).
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Identifier
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AAI8508691
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identifier
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8508691
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Creator
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CORY, ROBERT N.
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Contributor
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Roman Osman Saul Maayani
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Date
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1985
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Language
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English
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Publisher
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City University of New York.
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Subject
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Health Sciences, Pharmacology
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Abstract
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Both the alpha-1 adrenergic and serotonergic receptor mediated responses of the rabbit aorta were separated into a phasic and tonic response by virtue of their different dependence on extracellular calcium concentration. The kinetics of each response was characterized with respect to its dependence on both the concentration of drug and calcium. 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 the concentrations of drug and calcium, its rate constant for onset does not depend on the concentration of calcium in the preincubation buffer. This rate constant of onset is not saturable with respect to drug concentration suggesting 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 the concentrations of drug and extracellular calcium. The rate constant for the generation of the tonic response depends on drug concentration in a saturable manner and linearly on extracellular calcium concentration. This suggests that the rate - determining step is 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 show that the efficacy of a drug in this system is the maximal rate of activation of the effector by the drug - receptor complex. It was shown that this efficacy term depends explicitly on the total number of receptors and implicitly on the nature of the drug.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
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Program
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Biomedical Sciences
