Circadian-phase-dependency in [3H]-dihydroalprenolol binding to rat heart ventricular membranes.
Binding studies with the beta-adrenoceptor antagonist ligand [3H]-dihydroalprenolol ([3H]-DHA, spec. act, 90-102 Ci/mmol) were performed with ventricular membranes L-D-synchronized (L:0.7-19 hr, D:-07 hr) male rats, sacrificed either at 08 hr or at 20 hr. Saturation experiments with crude or washed and preincubated membranes revealed two affinity states of specific [3H]-DHA binding which were abolished after addition of the guanine nucleotide Gpp(NH)p. In crude membranes the apparent Bmax-value at 20 hr was about 40% higher than at 08 hr, in washed and preincubated membranes the nocturnal increase in the apparent Bmax-value was not observed. Pretreatment of rats with isoprenaline (50 mg/kg, i.p.) decreased and catecholamine depletion (reserpine plus inhibition of tyrosine-hydroxylase) increased Bmax-values in crude membranes. The circadian-stage-dependent and the drug-induced effects on the apparent number of beta-adrenoceptors are assumed to be due to circadian or drug-induced variations in the turnover of cardiac noradrenaline.
D000526:Alprenolol / Q000031:analogs & derivatives*; D000818:Animals; D002940:Circadian Rhythm; D004082:Dihydroalprenolol / Q000378:metabolism*; D006150:Guanine Nucleotides / Q000494:pharmacology; D006352:Heart Ventricles; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D012110:Reserpine / Q000494:pharmacology; D012508:Sarcolemma / Q000378:metabolism
D006150:Guanine Nucleotides; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D000526:Alprenolol; D012110:Reserpine; D007545:Isoproterenol