Alterations in leukocyte beta-receptor affinity with aging. A potential explanation for altered beta-adrenergic sensitivity in the elderly.
The elderly have reduced beta-adrenergic sensitivity to agonists, but no change in receptor density. We investigated the relation between beta-receptor affinity for agonists and age in beta-receptors on lymphocytes from 20 healthy men 21 to 74 years old. As an index of beta-receptor affinity for agonists, we determined the IC50 of isoproterenol--the concentration of isoproterenol required to inhibit 50 per cent of iodohydroxybenzylpindolol binding in vitro. We found that receptor affinity for agonists was correlated with age and plasma norepinephrine concentration. Twelve subjects (six 21 to 29 years old and six 55 to 74 years old) were also studied in both the supine and upright positions. In samples obtained in the supine position, the proportion of receptors binding agonist with a high affinity was decreased in the older subjects as compared with the young subjects (22 +/- 1 per cent vs. 38 +/- 3 per cent; P less than 0.05). With upright posture and the associated acute elevation of endogenous plasma catecholamines, the proportion of receptors binding agonist with a high affinity was reduced in the young; no such changes were seen in the older subjects. The data suggest that reduced beta-receptor affinity for agonists may be an explanation for altered beta-adrenergic sensitivity in the elderly.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000375:Aging; D004837:Epinephrine / Q000097:blood; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011187:Posture; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D011943:Receptors, Adrenergic, beta; C011878:iodohydroxybenzylpindolol; D010869:Pindolol; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine