Chronic beta 1-adrenoceptor antagonist treatment sensitizes beta 2-adrenoceptors, but desensitizes M2-muscarinic receptors in the human right atrium.
1. In 64 patients undergoing coronary artery bypass grafting the effects of chronic beta 1-adrenoceptor antagonist (metoprolol, atenolol, bisoprolol) treatment on right atrial beta-adrenoceptor and muscarinic M2-receptor number and functional responsiveness were investigated. 2. The beta 1-adrenoceptor antagonists increased right atrial beta 1-adrenoceptor number, did not affect beta 2-adrenoceptor number, and decreased muscarinic M2-receptor number. 3. Concomitantly, activation of right atrial adenylate cyclase by 10 microM GTP, 10 microM isoprenaline and 1 microM forskolin was enhanced and inhibition by 100 microM carbachol was diminished. 4. On isolated, electrically driven right atria the beta 1-adrenoceptor-mediated positive inotropic effect of noradrenaline was - even with beta 1-adrenoceptor number increased - not altered, while the beta 2-adrenoceptor-mediated effect of procaterol was markedly enhanced. However, the carbachol-induced negative inotropic effect was decreased. 5. It is concluded that chronic beta 1-adrenoceptor antagonist treatment increases beta 1-adrenoceptor number and concomitantly sensitizes beta 2-adrenoceptor function, but desensitizes muscarinic M2-receptor function in the human heart.
Motomura
S
S
Biochemical Research Laboratory, Medizinische Klinik & Poliklinik, University of Essen, F.R.G.
Deighton
N M
NM
Zerkowski
H R
HR
Doetsch
N
N
Michel
M C
MC
Brodde
O E
OE
D000067956:Adenylyl Cyclase Inhibitors; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D002217:Carbachol / Q000037:antagonists & inhibitors; D005260:Female; D006325:Heart Atria / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013997:Time Factors
D000067956:Adenylyl Cyclase Inhibitors; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D002217:Carbachol