Dexamethasone-induced increase in lymphocyte beta-adrenergic receptor density and cAMP formation in vivo.
The influence of dexamethasone on the density of beta(2)-adrenergic receptors (beta(2)-adrenergic receptors (beta(2)AR) and on the intracellular adenosine 3',5'-cyclic monophosphate (cAMP) response was studied in equine lymphocytes in vivo. Dexamethasone (0.1 mg/kg/day, 1-5 days) raised the number of beta(2)AR - B(max) as assessed by (-)-[(125)I]iodocyanopindolol binding (ICYP) - to 2.5- to 3.5-fold as compared with control values. The increase in beta(2)AR number was fast (342 +/- 49 vs. 960 +/- 103 binding sites/lymphocyte after 24 h), reaching a maximum between 48 and 96 h (342 +/- 49 vs. 1,289 +/- 150 and 1,106 +/- 68 binding sites/lymphocyte, respectively). The isoprenaline-induced cAMP accumulation (measured by a [(3)H]-cAMP radioimmunoassay system) was concomitantly enhanced by dexamethasone (1.5- to 2.4-fold). Both parameters were reversible to a similar rate at dexamethasone withdrawal. The changes in the functional responsiveness of lymphocytes were not reflected by changes in the binding affinity for ICYP of beta(2)AR. These results demonstrate the in vivo glucocorticoid-mediated regulation of beta(2)AR in equine lymphocytes which has already been suggested on the basis of in vitro observations in other tissues.
Abraham
G
G
Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, Germany.
Schusser
G F
GF
Ungemach
F R
FR
D000818:Animals; D001665:Binding Sites; D000242:Cyclic AMP / Q000378:metabolism*; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006736:Horses; D007275:Injections, Intravenous; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D011869:Radioligand Assay; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D005938:Glucocorticoids; D011943:Receptors, Adrenergic, beta; D003907:Dexamethasone; D000242:Cyclic AMP