title: Enhancement of beta-adrenergic-induced cAMP accumulation in activated T-cells.
abstract: Agonist stimulation of the beta-adrenergic receptor on T-cells results in the production of cAMP, which has been correlated with modulation of T-cell function. In previous studies, we have demonstrated that the mitogen PHA can synergistically enhance the accumulation of cAMP in T-cells in response to the agonist isoproterenol. In this report we have investigated the mechanisms by which dual stimulation of T-cells acts to synergistically enhance cAMP accumulation. The results demonstrate that increasing the levels of intracellular calcium with ionomycin or thapsigargin enhanced isoproterenol-induced cAMP accumulation in T-cells. In contrast, PHA enhanced isoproterenol-induced cAMP by a calcium-independent mechanism as evidenced by stimulation with isoproterenol plus PHA in calcium-free medium. Further studies revealed that PHA prevented both sequestration of the beta-adrenergic receptor and its dissociation from Gs protein in response to isoproterenol stimulation. In contrast, PHA did not prevent the functional uncoupling of the beta-adrenergic receptor from adenylyl cyclase, suggesting that additional mechanisms are likely involved. In summary, these studies demonstrate that dual receptor signalling of T-cells increases cAMP accumulation and offers a potential mechanism for catecholamine modulation of T-cell function.
authors.affiliation: Department of Microbiology and Immunology, University of Kentucky Medical Center, Lexington 40536-0084.
authors.forename: S L
authors.initials: SL
authors.lastname: Carlson
authors.forename: K
authors.initials: K
authors.lastname: Trauth
authors.forename: W H
authors.initials: WH
authors.lastname: Brooks
authors.forename: T L
authors.initials: TL
authors.lastname: Roszman
mesh_terms: D002118:Calcium / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation; D010835:Phytohemagglutinins / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism / Q000502:physiology*; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D008024:Ligands; D010835:Phytohemagglutinins; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D002118:Calcium