Enhancement of β-Adrenergic-induced cAMP accumulation in activated T-Cells

✍ Scribed by Dr. Sonia L. Carlson; Konrad Trauth; William H. Brooks; Thomas L. Roszman

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: English
• Weight: 1011 KB
• Volume: 161
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041610106

✦ Synopsis

Agonist stimulation of the P-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 calciumfree medium. Further studies revealed that PHA prevented both sequestration of the P-adrenergic receptor and its dissociation from Gs protein in response to isoproterenol stimulation. In contrast, PHA did not prevent the functional uncoupling of the P-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.