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 microM 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 microM 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-regulated 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.(ABSTRACT TRUNCATED AT 250 WORDS)
D000375:Aging; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004082:Dihydroalprenolol / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000503:physiopathology*; D013997:Time Factors
D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D004082:Dihydroalprenolol; D011433:Propranolol; D000242:Cyclic AMP; D007545:Isoproterenol; C033394:CGP 12177