Regulation of beta adrenergic receptors on rat mononuclear leukocytes by stress: Receptor redistribution and down-regulation are altered with aging

In vitro incubation of mononuclear leukocytes (MNL) with catecholamines desensitizes beta adrenergic receptors, meaning isoproterenol-stimulated cyclic AMP accumulation decreases. This desensitization is accompanied by two patterns of receptor changes: first, reduction of surface receptors (defined as binding of [³H]dihydroalprenolol inhibited by 1 μM CGP 12177 [4-(3-tertiarybutylamino-2-hydroxypropoxy)-benzimidazole-2-on- hydrochloride]) without any change in the total number of [³H] dihydroalprenolol binding sites inhibited by 1 μM propranolol (receptor redistribution); then reduction of the total number of receptors (receptor down-regulation). In the present study we investigated receptor redistribution and down-regulation under physiological conditions by raising endogenous catecholamines in the rat by stress. In young rats a single immobilization stress induced MNL beta adrenergic receptor redistribution: the number of surface receptors was reduced by about 50% but the total number remained the same. Receptor redistribution was prevented completely in rats pretreated with beta-blocking nadolol. Repeated stress down-regulation the MNL beta adrenergic receptors as shown by a reduction in the total number of sites. We also investigated the regulation of beta adrenergic receptors in three age-groups. After 60 min of immobilization stress the number of MNL surface receptors was reduced in young (4-month-old) rats but not in mature (12-month-old) or aged (26-month-old) rats. Using an alternative stress procedure, after single or repeated open-field sessions, we found receptor redistribution and down-regulation, respectively, in young rats. None of these adaptive receptor response was observed in 26-month-old rats. We conclude that beta adrenergic receptor redistribution and down-regulation can occur under physiological conditions and that these adaptive receptor changes are impaired with aging.