High Affinity Platelet 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 3Hbromoxidine 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 (3Hyohimbine Bmax: Young: 140 +/- 10 vs Old: 135 +/- 9 fmol/mg protein; p = .71), receptor density for 3Hbromoxidine 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.