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Sensitization by dexamethasone of lymphocyte cyclic AMP formation: evidence for increased function of the adenylyl cyclase catalyst
Author(s) -
Michel Martin C.,
Knapp Jörg,
Ratjen Hanna
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb16200.x
Subject(s) - adenylyl cyclase , forskolin , medicine , endocrinology , adcy9 , gs alpha subunit , cholera toxin , adcy10 , cyclase , cyclic adenosine monophosphate , camp dependent pathway , chemistry , isoprenaline , biology , receptor , stimulation
1 Glucocorticoids and elevations of intracellular adenosine 3′:5′‐cyclic monophosphate (cyclic AMP) may affect lymphocyte activation, proliferation and effector functions in similar ways. Therefore, we have investigated the effects of the glucorticoid, dexamethasone, on human lymphocyte cyclic AMP formation. 2 Treatment of resting human lymphocytes with the glucocorticoid, dexamethasone, sensitized prostaglandin E 2 ‐stimulated cyclic AMP accumulation in a time‐ and concentration‐dependent manner. 3 In membranes of lymphocytes treated for 24 h with 100 n m dexamethasone, maximal adenylyl cyclase activity stimulated by prostaglandin E 2 , isoprenaline, guanosine 5′‐triphosphate (GTP), forskolin and MnCl 2 was significantly enhanced; the EC 50 for these agents was not significantly altered. 4 β 2 ‐Adrenoceptor density, immunodetectable α‐subunits of the G‐proteins G s and G i , and pertussis toxin‐substrates were not significantly altered by dexamethasone treatment. 5 In dexamethasone‐treated lymphocytes, prostaglandin E 2 ‐mediated inhibition of concanavalin A‐induced Ca 2+ elevations was doubled compared to control cells. 6 Based on these data and the observation that enhancement of forskolin‐ and MnCl 2 ‐stimulated adenylyl cyclase activity could quantitatively account for the enhancement of prostaglandin E 2‐ , isoprenaline‐ or GTP‐stimulated adenylyl cyclase activity, we conclude that dexamethasone treatment sensitizes cyclic AMP formation in resting human lymphocytes by altering the adenylyl cyclase catalyst rather than G‐proteins or hormone receptors. This results in an enhanced capability of cyclic AMP generating agonists to inhibit early steps of lymphocyte activation.