Mechanisms of the circadian regulation of beta-adrenoceptor density and adenylyl cyclase activity in cardiac tissue from normotensive and spontaneously hypertensive rats.
Circadian variation in beta-adrenoceptor density and adenylyl cyclase activity was studied in myocardium from normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). In SHR cardiac beta-adrenoceptor density was significantly lower than in WKY. This reduction in total beta-adrenoceptors was exclusively due to a loss in the beta 1-subtype. Total and beta 1-adrenoceptor density in ventricles from both strains exhibited significant circadian variation with peaks occurring in the middle of the light and dark periods, whereas the beta 2-subtype did not show rhythmicity. Similarly, stimulation of adenylyl cyclase via total beta-adrenoceptors and via the beta 1-subtype was circadian time dependent, but circadian peaks occurring at the beginning of the light and dark periods were 6 h apart from those in beta-adrenoceptor density. Rhythmicity in the formation of cAMP was observed under basal conditions and after stimulation by isoprenaline or a forskolin derivative, whereas addition of manganese-ions abolished the circadian variation. In conclusion, the present study demonstrates that in ventricular tissue from WKY and SHR circadian rhythms observed in total beta-adrenoceptor density are due exclusively to variations in the beta 1-subtype. Since peaks in cAMP formation coincided with troughs in beta-adrenoceptor number, cAMP mediated phosphorylation of beta-adrenoceptors enhancing their down-regulation, could be involved in the circadian regulation of myocardial beta-adrenoceptor density. Rhythmicity in cAMP formation itself seems to involve coupling of G-proteins, because manganese ions abolished the circadian variation.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D006352:Heart Ventricles; D006973:Hypertension / Q000201:enzymology / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction
D011943:Receptors, Adrenergic, beta; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D008274:Magnesium