The effect of acidosis on beta-adrenergic receptors in ferret cardiac muscle.
Acidosis decreases the force of contraction of cardiac muscle in response to noradrenaline. The role of beta-adrenergic receptors in this response to acidosis was investigated. Radioligand techniques were used to determine beta-adrenergic receptor number and the degree of G-protein coupling, and to see whether these were altered in tissues subject to acidosis. The effect of pH on agonist and antagonist binding to these receptors was also investigated. Tissue pre-exposure to acidic conditions had no effect on numbers of beta-adrenergic receptors and no effect on the affinity of [125I]iodocyanopindolol (ICYP) for the receptors. Agonist competition experiments indicated that there was no change in the affinity of isoprenaline for these receptors, and there was no change in the relative proportions of high and low affinity binding sites. When radioligand experiments were performed under acidic conditions, however, the total number of beta-adrenergic receptors increased, and the affinity of these receptors for isoprenaline increased. This increase in agonist affinity might, therefore, minimize the shift to the right seen in the dose-response curve to noradrenaline during acidosis.
Department of Physiology, University of Leeds.
A J
AJ
Nimmo
N
N
Than
C H
CH
Orchard
E M
EM
Whitaker
D000138:Acidosis / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D005289:Ferrets; D019204:GTP-Binding Proteins / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000378:metabolism; D007700:Kinetics; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology; D010210:Papillary Muscles / Q000187:drug effects / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; D019204:GTP-Binding Proteins; D007545:Isoproterenol; D009638:Norepinephrine