High affinity platelet alpha 2-adrenergic receptor density is decreased in older humans.
We have previously found that elderly humans have increased plasma norepinephrine (NE) levels and reduced alpha 2-adrenergic receptor-mediated inhibition of platelet membrane adenylyl cyclase activity. One possible mechanism for the latter finding is a decrease of high affinity platelet alpha 2-adrenergic receptor density in the elderly. To test this possibility, we used the alpha 2-adrenergic receptor agonist radioligand [3H]bromoxidine to define platelet alpha 2-adrenergic receptor high affinity binding sites in 31 young (age 19-31 yr) and 25 older (age 61-75 yr) normal human subjects. Plasma NE levels were higher (1.65 +/- 0.44 vs 1.12 +/- 0.37 nM; p = .0001) and epinephrine (EPI)-mediated adenylyl cyclase inhibition was lower in the older group (40 +/- 2 vs 50 +/- 2% inhibition at 10(-4) M EPI; p = .04). Although total platelet alpha 2-adrenergic receptor density was similar ([3H]yohimbine Bmax: Young: 140 +/- 10 vs Old: 135 +/- 9 fmol/mg protein; p = .71), receptor density for [3H]bromoxidine was significantly lower in the older group (30 +/- 3 vs 42 +/- 4 fmol/mg protein; p = .02). We conclude that there is an age-associated decrease in high affinity platelet alpha 2-adrenergic receptor density in humans which may contribute to the age-associated reduction in receptor-mediated inhibition of adenylyl cyclase.
Supiano
M A
MA
Institute of Gerontology, University of Michigan, Ann Arbor.
Hogikyan
R V
RV
D000262:Adenylyl Cyclases / Q000378:metabolism; D000316:Adrenergic alpha-Agonists; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D000068438:Brimonidine Tartrate; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008566:Membranes / Q000378:metabolism; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D011810:Quinoxalines; D011869:Radioligand Assay; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D000068438:Brimonidine Tartrate; D000262:Adenylyl Cyclases; D009638:Norepinephrine