Carlson S L, Trauth K, Brooks W H, Roszman T L
Department of Microbiology and Immunology, University of Kentucky Medical Center, Lexington 40536-0084.
J Cell Physiol. 1994 Oct;161(1):39-48. doi: 10.1002/jcp.1041610106.
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.
激动剂刺激T细胞上的β-肾上腺素能受体会导致环磷酸腺苷（cAMP）的产生，这与T细胞功能的调节相关。在先前的研究中，我们已经证明丝裂原植物血凝素（PHA）可以协同增强T细胞中cAMP对激动剂异丙肾上腺素的积累反应。在本报告中，我们研究了T细胞双重刺激协同增强cAMP积累的机制。结果表明，用离子霉素或毒胡萝卜素提高细胞内钙水平可增强异丙肾上腺素诱导的T细胞cAMP积累。相比之下，PHA通过一种不依赖钙的机制增强异丙肾上腺素诱导的cAMP，这在无钙培养基中用异丙肾上腺素加PHA刺激时得到证明。进一步的研究表明，PHA可防止β-肾上腺素能受体的隔离及其在异丙肾上腺素刺激下与Gs蛋白的解离。相比之下，PHA不能阻止β-肾上腺素能受体与腺苷酸环化酶的功能性解偶联，这表明可能涉及其他机制。总之，这些研究表明T细胞的双受体信号传导增加了cAMP积累，并为儿茶酚胺调节T细胞功能提供了一种潜在机制。
