Mechanisms of the circadian regulation of β-adrenoceptor density and adenylyl cyclase activity in cardiac tissue from normotensive and spontaneously hypertensive …

K Witte, R Parsa-Parsi, M Vobig, B Lemmer - Journal of molecular and …, 1995 - Elsevier
K Witte, R Parsa-Parsi, M Vobig, B Lemmer
Journal of molecular and cellular cardiology, 1995Elsevier
Circadian variation in β-adrenoceptor density and adenylyl cyclase activity was studied in
myocardium from normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive
rats (SHR). In SHR cardiac β-adrenoceptor density was significantly lower than in WKY. This
reduction in total β-adrenoceptors was exclusively due to a loss in the β1-subtype. Total and
β1-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 β2 …
Circadian variation in β-adrenoceptor density and adenylyl cyclase activity was studied in myocardium from normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). In SHR cardiac β-adrenoceptor density was significantly lower than in WKY. This reduction in total β-adrenoceptors was exclusively due to a loss in the β1-subtype. Total and β1-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 β2-subtype did not show rhythmicity. Similarly, stimulation of adenylyl cyclase via total β-adrenoceptors and via the β1-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 β-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 β-adrenoceptor density are due exclusively to variations in the β1-subtype. Since peaks in cAMP formation coincided with troughs in β-adrenoceptor number, cAMP mediated phosphorylation of β-adrenoceptors enhancing their down-regulation, could be involved in the circadian regulation of myocardial β-adrenoceptor density. Rhythmicity in cAMP formation itself seems to involve coupling of G-proteins, because manganese ions abolished the circadian variation.
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