Beta-adrenergic receptors on human lymphocytes: comparison of down-regulation in vivo and in vitro.
beta-Adrenergic receptors on isolated human lymphocytes were enumerated using 125I-cyanopindolol (125I-CYP), after a 90-min exposure to 50 mumols/l l-isoproterenol in vitro. No change in receptor density could be shown in assays performed at 37 degrees C, although a 40% reduction was apparent in binding studies carried out at 4 degrees C. In contrast, beta-adrenergic receptors on lymphocytes from mild asthmatics after a 3-week course of oral terbutaline showed a 40% reduction in receptor density regardless of the assay temperature, in addition to a 2.5-fold reduction in the receptor affinity for isoproterenol. The data are consistent with reports that a fraction of receptors are sequestered during short-term exposure to agonists. Sequestered receptors may or may not be detected by radioligand binding assays depending on the ligand of choice, temperature of the binding assay and duration of prior exposure to the agonist. After extended exposure to an agonist in vivo, the number of surface receptors was reduced, and sequestered receptors were not present, presumably as a result of degradation.
Borst
S E
SE
Division of Clinical Pharmacology, UCLA School of Medicine.
Hui
K K
KK
Conolly
M E
ME
D000319:Adrenergic beta-Antagonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D013726:Terbutaline / Q000494:pharmacology; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; C047975:cyanopindolol; D010869:Pindolol; D007545:Isoproterenol; D013726:Terbutaline