beta-Adrenergic and muscarinic receptor expression are regulated in opposite ways during senescence in rat left ventricle.
The well-known attenuated sensitivity of senescent heart to isoproterenol is accompanied by a decreased beta1-adrenergic receptors (beta1-AR) density, a down regulation process which may involve several molecular modifications and whose understanding is incomplete. Data concerning the M2-R muscarinic receptors (M2-R) are more contradictory. Both the absolute and relative concentrations of beta1-AR and M2-R as well as the coupling protein G alpha s and G alpha(i2) mRNAs were determined by slot-blot analysis in the left ventricles (LVs) of 6-7 week and 22-month-old male Wistar rats. In addition, the beta-AR and M2-R densities were quantitated by radioactive ligand binding. (1) The M2-R mRNA concentration increases by 92+/-32% in senescent as compared to adult animals; by contrast, the density in M2-R remains unchanged, suggesting that the M2-R expression was not exclusively regulated at a pre-translational level. (2) The beta1-AR mRNA concentration was nearly halved (reduced by 46+/-9.5%) and paralleled the 51+/-5.6% diminution of the beta-AR density which resulted exclusively from the decrease of beta1-AR density without change in the beta2-AR concentration, suggesting a pre-translational regulation of the beta1-AR expression. (3) G alpha(i2) mRNA concentration was unchanged, while G alpha s mRNA concentration was reduced by 26+/-4.6% in senescent compared with adult LVs. To conclude, the different components of the adrenergic and muscarinic systems are differentially regulated during aging.
Hardouin
S
S
INSERM U 127 Hôpital Lariboisière, Paris, France.
Mansier
P
P
Bertin
B
B
Dakhly
T
T
Swynghedauw
B
B
Moalic
J M
JM
D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000096:biosynthesis; D019204:GTP-Binding Proteins / Q000096:biosynthesis; D006352:Heart Ventricles / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D018342:Receptors, Adrenergic, beta-1 / Q000096:biosynthesis*; D011976:Receptors, Muscarinic / Q000096:biosynthesis*
D011518:Proto-Oncogene Proteins; D018342:Receptors, Adrenergic, beta-1; D011976:Receptors, Muscarinic; D019204:GTP-Binding Proteins; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs; C498017:Gnai2 protein, rat