Age-related changes in [3H]prazosin binding and phosphoinositide hydrolysis in rat ventricular myocardium.
1. We investigated, using rats at 2, 12 and 24 months of age, the effect of aging on ventricular alpha 1-adrenoceptor responsiveness by measuring the [3H]prazosin binding, [3H]inositol phosphate formation, the cholesterol/phospholipid ratio and membrane viscosity. 2. The density of specific [3H]prazosin binding sites on membranes was significantly reduced with advanced age, and the binding affinity for [3H]prazosin was significantly increased. 3. Norepinephrine (NE)-induced formation of [3H]inositol phosphates in slices was also reduced with advanced age. However, the EC50 for NE stimulation of [3H]inositol phosphates was significantly higher when compared to those at adult ages. 4. The cholesterol content in membranes was significantly decreased with advanced age; concomitantly, a decrease in the cholesterol/phospholipid ratio was observed. The membrane viscosity as measured by using 1,6-diphenyl-1,3,5-hexatriene significantly decreased with advanced age. 5. These results suggest that the altered cholesterol/phospholipid ratio and/or the membrane viscosity during aging may account for the increase in the binding affinity for [3H]prazosin and/or the reduced responsiveness of aged ventricular myocardium to NE.
Miyamoto
A
A
Department of Pharmacology, Sapporo Medical College, Japan.
Ohshika
H
H
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006868:Hydrolysis; D008297:Male; D008566:Membranes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism; D014783:Viscosity
D010716:Phosphatidylinositols; D010743:Phospholipids; D011942:Receptors, Adrenergic, alpha; D002784:Cholesterol; D009638:Norepinephrine; D011224:Prazosin