原创力文档receptor-mediated enhancement of beta adrenergic drug activity by ascorbate in vitro and in vivoβ肾上腺素能药物活性的受体介导增强抗坏血酸盐在体外和体内.pdfVIP
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receptor-mediated enhancement of beta adrenergic drug activity by ascorbate in vitro and in vivoβ肾上腺素能药物活性的受体介导增强抗坏血酸盐在体外和体内
Receptor-Mediated Enhancement of Beta Adrenergic
Drug Activity by Ascorbate In Vitro and In Vivo
1 1 2 3
Patrick F. Dillon , Robert Root-Bernstein *, N. Edward Robinson , William M. Abraham , Catherine
Berney2
1 Department of Physiology, Michigan State University, East Lansing, Michigan, United States of America, 2 Department of Large Animal Clinical Science, Michigan State
University, East Lansing, Michigan, United States of America, 3 Department of Research, Mount Sinai Medical Center, Miami Beach, Florida, United States of America
Abstract
Rationale: Previous in vitro research demonstrated that ascorbate enhances potency and duration of activity of agonists
binding to alpha 1 adrenergic and histamine receptors.
Objectives: Extending this work to beta 2 adrenergic systems in vitro and in vivo.
Methods: Ultraviolet spectroscopy was used to study ascorbate binding to adrenergic receptor preparations and peptides.
Force transduction studies on acetylcholine-contracted trachealis preparations from pigs and guinea pigs measured the
effect of ascorbate on relaxation due to submaximal doses of beta adrenergic agonists. The effect of inhaled albuterol with
and without ascorbate was tested on horses with heaves and sheep with carbachol-induced bronchoconstriction.
Measurements: Binding constants for ascorbate binding to beta adrenergic receptor were derived from concentration-
dependent spectral shifts. Dose- dependence curves were obtained for the relaxation of pre-contracted trachealis
preparations due to beta agonists in the presence and absence of varied ascorbate. Tachyphylaxis and fade were also
measured. Dose response curves were determined for the effect of albuterol plus
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