Evidence for a circadian-phase-dependency in 3H-dihydroalprenolol binding and cyclic AMP content in heart ventricles of L-D-synchronized rats.
Receptor binding studies with 3H-dihydroalprenolol (3H-DHA, spec. act. 90-102 Ci/mmol) were performed in heart ventricular membranes of light-dark-synchronized (L: 7-19 h, D: 19-7 h) male rats, which were sacrificed either at 08:00 h or 20:00 h. Saturation, competition and kinetic studies revealed two specific 3H-DHA binding sites--being specific for mainly beta 1-adrenoceptors--which were abolished after addition of the guanine nucleotide Gpp(NH)p. In control experiments, i.e. in the absence of the guanine nucleotide, circadian-phase-dependent differences in the KD and Bmax values were observed. Total number of binding sites was about 40% higher in the 20:00 h-ventricles than in the 08:00 h-ventricles. Pretreatment with isoprenaline further decreased and catecholamine-depletion further increased Bmax values. In accordance with these findings a significant circadian rhythm in the ventricular cAMP content with a maximum at 20:00 h and a minimum at 08:00 h was observed.
D000526:Alprenolol / Q000031:analogs & derivatives*; D000818:Animals; D002940:Circadian Rhythm; D000242:Cyclic AMP / Q000378:metabolism*; D004082:Dihydroalprenolol / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012110:Reserpine / Q000494:pharmacology
D004082:Dihydroalprenolol; D000526:Alprenolol; D012110:Reserpine; D000242:Cyclic AMP; D007545:Isoproterenol