Effects of chronic pindolol treatment on human myocardial beta 1- and beta 2-adrenoceptor function.
To evaluate the effects of chronic pindolol treatment on human myocardial beta-adrenoceptor, membrane preparations from right atrial auricles from patients on chronic pindolol treatment and from patients not treated with beta-blocker were compared with respect to specific binding of [125I]-iodocyanopindolol [( 125I]-ICYP) and adenylate cyclase (AC) activity. Pindolol treatment was associated with a 25% increase in total beta-adrenoceptor density (72.3 vs. 58.3 fmol/mg protein). This increase was due a 40% increase of the beta 1-adrenoceptor subtype (62.2 vs. 44.3 fmol/mg protein), while beta 2-adrenoceptor density was decreased by about 25% (10.0 vs. 14.0 fmol/mg). Isoprenaline 5 mumol/l (9.7 vs. 14.2 pmol/min/mg) and terbutaline 50 mumol/l (4.9 vs. 8.3 pmol/min/mg protein) stimulated adenylate cyclase activity was reduced, whereas fluoride (10 mmol/l) stimulated cAMP production to the same extent in both groups (9.4 vs 9.4 pmol/min/mg protein). Thus, chronic treatment with pindolol was associated with upregulation of the beta 1-adrenoceptors and a down-regulation of the beta 2-adrenoceptors. The total level of beta-adrenoceptors was slightly increased. In spite of this, adenylate cyclase activity and response was reduced.
Bjørnerheim
R
R
Medical Department B, Rikshospitalet University Hospital, Olso, Norway.
Golf
S
S
Hansson
V
V
D000262:Adenylyl Cyclases / Q000378:metabolism; D000368:Aged; D000242:Cyclic AMP / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D020120:Iodocyanopindolol; D007545:Isoproterenol; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives / Q000494:pharmacology*; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013726:Terbutaline; D015854:Up-Regulation / Q000187:drug effects
D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D010869:Pindolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D013726:Terbutaline