Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Granulomas develop around schistosome ova in murine Schistosoma mansoni. These granulomas have eosinophils that produce VIP. It is possible that VIP participates in immunoregulation. VIP-mediated effects usually operate through a cAMP-dependent mechanism. To identify VIP-responsive inflammatory cells in murine schistosomiasis, inflammatory cells were exposed to VIP and assessed for adenylate cyclase activation and VIP binding. VIP increased adenylate cyclase activity in splenic lymphocytes from both normal and infected mice. In each case, the half-maximal stimulation was at about 5 x 10(-8) M. [125I]VIP bound to splenic lymphocytes specifically, with a Kd of 10(-8) M. This suggested that maximal adenylate cyclase activation requires full receptor occupancy. The receptor was highly specific for VIP. Hormone analogs, that are VIP receptor antagonists in some tissues, were only weak agonists of the lymphocyte VIP receptor. Granuloma cells also bound VIP and responded with adenylate cyclase activation in a manner similar to that of spleen cells. Both splenic T and B lymphocytes responded to VIP. Deletion experiments, using anti-Thy 1.2, suggested that most of the responsive granuloma cells were T lymphocytes. Thus, VIP alters cAMP metabolism in granuloma T cells through a receptor-coupled mechanism similar to that observed for spleen cells. Binding studies on mouse intestinal epithelial cells suggested that their VIP receptor is functionally and possibly structurally different from the VIP receptor on mouse lymphocytes. Additional experiments suggested that VIP and other neuropeptides are unlikely to alter the granulomatous response through a primary interaction with the granuloma macrophages.
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PMID:Granulomas in murine schistosomiasis mansoni contain vasoactive intestinal peptide-responsive lymphocytes. 167 41

The anti-inflammatory effects of E-prostaglandins (PGE) are attracting interest because they are mediated through actions on cells which are also targets for the putative immunomodulator functions of PGE. In the majority of experimental inflammatory conditions, in which inhibitory effects of PGE have been demonstrated, a variety of immunocytes are implicated, including diverse lymphocyte populations. The inhibitory effects of PGE, however, are also readily observable on the tissue component of the carrageenin-induced granuloma (an immune-related inflammatory model) in which activated macrophages, but not lymphocytes participate. Granuloma-derived macrophages are particularly interesting cells for the study of responsiveness to PGE, because the results obtained on such cells in vitro are directly related to the anti-inflammatory effects of PGE on the macrophage phase of the granuloma in vivo. Such combined studies have revealed differences between the responsiveness of granuloma macrophages to PGE2 and prostacyclin, while with elicited peritoneal macrophages such a difference could not be observed. The adenylate cyclase in granuloma macrophages appears to be unusually sensitive to activation by PGE2, but insensitive to prostacyclin.
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PMID:Macrophages as targets of inhibitory effects of E-type prostaglandins in immune-related inflammation. 628 Apr 64