Alterations in leukocyte β-receptor affinity with aging: a potential explanation for altered β-adrenergic sensitivity in the elderly

Abstract The elderly have reduced β-adrenergic sensitivity to agonists, but no change in receptor density. We investigated the relation between β-receptor affinity for agonists and age in β-receptors on lymphocytes from 20 healthy men 21 to 74 years old. As an index of β-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<0.05). With upright posture and the associated acute elevation of endogenous plasma catecholamines, the p...

[1]  R. Feldman,et al.  Dynamic regulation of leukocyte beta adrenergic receptor-agonist interactions by physiological changes in circulating catecholamines. , 1983, The Journal of clinical investigation.

[2]  P. Molinoff,et al.  Decreased beta adrenergic receptor density on human lymphocytes after chronic treatment with agonists. , 1983, The Journal of pharmacology and experimental therapeutics.

[3]  I. Abrass,et al.  Catalytic unit of adenylate cyclase: reduced activity in aged-human lymphocytes. , 1982, The Journal of clinical endocrinology and metabolism.

[4]  J. Kelly,et al.  Human Lymphocyte β‐Adrenoceptor Density in Relation to Age and Hypertension , 1982 .

[5]  P. Molinoff,et al.  Changes in the density of beta adrenergic receptors in rat lymphocytes, heart and lung after chronic treatment with propranolol. , 1982, The Journal of pharmacology and experimental therapeutics.

[6]  R. Lefkowitz,et al.  Validation and statistical analysis of a computer modeling method for quantitative analysis of radioligand binding data for mixtures of pharmacological receptor subtypes. , 1982, Molecular pharmacology.

[7]  R. Landmann,et al.  High affinity beta-2-adrenergic receptors in mononuclear leucocytes: similar density in young and old normal subjects. , 1981, Life sciences.

[8]  E. Braunwald,et al.  Decreased lymphocyte beta-adrenergic-receptor density in patients with heart failure and tolerance to the beta-adrenergic agonist pirbuterol. , 1981, The New England journal of medicine.

[9]  D. Robertson,et al.  Regulation of human leukocyte beta receptors by endogenous catecholamines: relationship of leukocyte beta receptor density to the cardiac sensitivity to isoproterenol. , 1981, The Journal of clinical investigation.

[10]  J. Krall,et al.  Age-related elevation of plasma catecholamine concentration and reduced responsiveness of lymphocyte adenylate cyclase. , 1981, The Journal of clinical endocrinology and metabolism.

[11]  I. Abrass,et al.  Human lymphocyte beta-adrenergic receptors are unaltered with age. , 1981, Journal of gerontology.

[12]  L. Limbird.  Activation and attenuation of adenylate cyclase. The role of GTP-binding proteins as macromolecular messengers in receptor--cyclase coupling. , 1981, The Biochemical journal.

[13]  R. Lefkowitz,et al.  A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupled beta-adrenergic receptor. , 1980, The Journal of biological chemistry.

[14]  K. O'malley,et al.  Age and beta adrenoceptor–mediated function , 1980, Clinical pharmacology and therapeutics.

[15]  O. Bertel,et al.  Decreased Beta‐Adrenoreceptor Responsiveness as Related to Age, Blood Pressure, and Plasma Catecholamines in Patients with Essential Hypertension , 1980, Hypertension.

[16]  R. Lefkowitz,et al.  A quantitative analysis of beta-adrenergic receptor interactions: resolution of high and low affinity states of the receptor by computer modeling of ligand binding data. , 1980, Molecular pharmacology.

[17]  R. Vestal,et al.  Reduced β‐adrenoceptor sensitivity in the elderly , 1979 .

[18]  G. Roth,et al.  Reduced β-adrenergic receptor concentrations in ageing man , 1977, Nature.

[19]  R. Lefkowitz,et al.  Identification of beta-adrenergic receptors in human lymphocytes by (-) (3H) alprenolol binding. , 1976, The Journal of clinical investigation.

[20]  E. Lakatta,et al.  Diminished Inotropic Response of Aged Myocardium to Catecholamines , 1975, Circulation research.

[21]  G. Roth.  Changes in hormone binding and responsiveness in target cells and tissues during aging. , 1975, Advances in experimental medicine and biology.

[22]  J. Peuler,et al.  A simplified radiometric assay for plasma norepinephrine and epinephrine. , 1973, Analytical biochemistry.

[23]  B. Brodie,et al.  Beta‐Receptor Activity in Aorta: Variations with Age and Species , 1970, Circulation research.

[24]  A. Bøyum,et al.  Isolation of mononuclear cells and granulocytes from human blood. , 1968 .

[25]  O. H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[26]  G. Scatchard,et al.  THE ATTRACTIONS OF PROTEINS FOR SMALL MOLECULES AND IONS , 1949 .