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Chronic β 1 ‐adrenoceptor antagonist treatment sensitizes β 2 ‐adrenoceptors, but desensitizes M 2 ‐muscarinic receptors in the human right atrium
Author(s) -
Motomura S.,
Deighton N.M.,
Zerkowski H.R.,
Doetsch N.,
Michel M.C.,
Brodde O.E.
Publication year - 1990
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1990.tb12715.x
Subject(s) - medicine , carbachol , muscarinic acetylcholine receptor , endocrinology , atenolol , antagonist , forskolin , muscarinic antagonist , isoprenaline , bisoprolol , chemistry , muscarinic acetylcholine receptor m2 , receptor , heart failure , stimulation , blood pressure
1 In 64 patients undergoing coronary artery bypass grafting the effects of chronic β 1 ‐adrenoceptor antagonist (metoprolol, atenolol, bisoprolol) treatment on right atrial β‐adrenoceptor and muscarinic M 2 ‐receptor number and functional responsiveness were investigated. 2 The β 1 ‐adrenoceptor antagonists increased right atrial β 1 ‐adrenoceptor number, did not affect β 2 ‐adrenoceptor number, and decreased muscarinic M 2 ‐receptor number. 3 Concomitantly, activation of right atrial adenylate cyclase by 10 μ m GTP, 10 μ m isoprenaline and 1 μ m forskolin was enhanced and inhibition by 100 μ m carbachol was diminished. 4 On isolated, electrically driven right atria the β 1 ‐adrenoceptor‐mediated positive inotropic effect of noradrenaline was — even with β 1 ‐adrenoceptor number increased — not altered, while the β 2 ‐adrenoceptor‐mediated effect of procaterol was markedly enhanced. However, the carbachol‐induced negative inotropic effect was decreased. 5 It is concluded that chronic β 1 ‐adrenoceptor antagonist treatment increases β 1 ‐adrenoceptor number and concomitantly sensitizes β 1 ‐adrenoceptor function, but desensitizes muscarinic M 2 ‐receptor function in the human heart.