Ageing and the alpha 2-adrenergic system of the platelet.
1. Platelets taken from healthy unmedicated subjects over 65 years of age display less inhibition of prostaglandin E1 (PGE1)-stimulated adenosine 3':5'-cyclic monophosphate (cyclic AMP) synthesis by noradrenaline than do platelets taken from young adults aged 18-25 years (P less than 0.03). The inhibition of cyclic AMP production by noradrenaline (10(-5) mol/l) correlates negatively with age over the range 18-92 years (r = -0.338, n = 108, P less than 0.005). The reduced cyclic AMP inhibition by noradrenaline in the elderly is not explained by basal cyclic AMP levels or degree of stimulation of platelets by PGE1, which do not differ between young and elderly subjects. The reduction itself is small, though, and cannot be demonstrated for a more potent agonist, adrenaline. 2. Despite the reduced noradrenaline response in the cyclic AMP system in the aged, platelet aggregation in response to alpha 2-adrenergic agents is normal or even slightly increased. Aggregation responses to adrenergic agents correlate well with aggregation responses to adenosine 5'-diphosphate, suggesting that the effector system is a major determinant of the aggregation response. 3. alpha 2-Adrenoceptor number measured by Scatchard analysis of equilibrium binding of [3H]yohimbine to platelet membranes is comparable in young and old subjects, and does not correlate with age. The KD for [3H]yohimbine does not correlate with age. The IC50 for noradrenaline displacing [3H]yohimbine is comparable in young and elderly subjects. Therefore the reduced inhibition of cyclic AMP production by noradrenaline in platelets from elderly subjects is not explained by changes in alpha 2-adrenoceptor number, or agonist- or antagonist-binding properties, but may reside in the coupling of receptor to cyclase.
Davis
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PB
Department of Pediatrics, Case Western Reserve University School of Medicine, Rainbow Babies and Childrens Hospital, Cleveland, Ohio.
Silski
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood*; D000527:Alprostadil / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008875:Middle Aged; D009638:Norepinephrine / Q000494:pharmacology; D010974:Platelet Aggregation; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*
D011942:Receptors, Adrenergic, alpha; D000242:Cyclic AMP; D000527:Alprostadil; D009638:Norepinephrine