Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclic GMP and activators (acetylcholine, E. coli heat-stable toxin) of guanylate cyclase were capable of completely replacing the helper cell or interleukin 2 requirement for gamma-interferon (IFN gamma) production by Lyt-1-,2+ cells from C57BL/6 mouse spleen cells. The cyclic GMP help was independent of DNA synthesis or proliferation in the IFN gamma-producing cells, because cyclic GMP reversed mitomycin C blockage of IFN gamma production but did not reverse the inhibition of DNA synthesis. Thus, the findings presented here are unrelated to the question of the second messenger role of cyclic GMP in the activation of lymphocytes for DNA synthesis and cellular proliferation. The cyclic GMP help for IFN gamma production was antagonized by cyclic AMP and inducers (isoproterenol) of adenylate cyclase.
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PMID:Cyclic GMP as the second messenger in helper cell requirement for gamma-interferon production. 629 93

Leukotrienes B4, C4, and D4 were capable of replacing the helper cell or interleukin 2 requirement for gamma-interferon (IFN gamma) production by Lyt-1-,2+ cells from C57BL/6 mouse spleen cells at leukotriene concentrations as low as 0.002 microM. An antioxidant inhibitor (butylated hydroxyanisole) of lipoxygenase metabolism of arachidonic acid suppressed IFN gamma production. The suppression was significantly reversed by leukotriene C4, which further suggests that leukotrienes and possibly other substances produced by the lipoxygenase pathway of arachidonic acid metabolism play an important role in the regulation of IFN gamma production. All of these events may be related to activation of guanylate cyclase activity, since cyclic GMP also significantly reversed the suppressor effects of butylated hydroxyanisole in IFN gamma production. The leukotriene help for IFN gamma production was independent of DNA synthesis or cellular proliferation. The data are consistent with the hypothesis that lipxoygenase products of arachidonic acid metabolism may play a role in the mediation of interleukin 2 help in IFN gamma production. Cells that are rich sources of leukotrienes, then, should play important roles in positive regulation of lymphokine production.
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PMID:Leukotrienes: positive signals for regulation of gamma-interferon production. 631 47

Several lines of evidence suggest that nitric oxide (NO), generated through nitric oxide synthase (NOS) by cleavage of terminal guanidino nitrogen from L-arginine, mediates tumor cell killing by mononuclear phagocytes. Natural killer (NK) cells are cytotoxic effector cells that lyse a variety of tumor and virus-infected cells in a MHC-unrestricted manner. NK cells cultured with interleukin 2 proliferate and acquire the ability to lyse a wide range of targets, including NK-resistant tumor cells (LAK activity). The present study was designed to investigate whether a NOS pathway exists in fresh or IL-2-activated NK cells and to assess the importance of NO synthesis in their activation and cytotoxic functions. NKR-P1 triggering, which is known to induce NK cell activation and mediate reverse ADCC, was able to induce arginine metabolism with consequent increase of nitrite and citrulline levels. Moreover, stimulated NO synthesis leads to guanylate cyclase activity with consequent cGMP generation. We also report that cytotoxic activities of fresh or IL-2-activated NK cells appear to be dependent on arginine levels in medium. Tumoricidal activity of both these effector cells, assessed against YAC-1 and P815 target cells, respectively, was indeed significantly reduced when cytotoxic assays were performed in arginine-free medium or in the presence of the L-arginine analog L-N-monomethyl-arginine, which inhibits nitroxide formation from L-arginine. Normal levels of cytotoxic activities could be restored by addition of exogenous L-arginine. NO generation by NK and LAK cells, determined as nitrite, citrulline, and cGMP synthesis, correlated well with their cytotoxic activities. Moreover, NOS activity gradually increased during the LAK generation and correlated well with the increasing capability of IL-2-activated NK cells to lyse NK-resistant targets, such as P815.
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PMID:Induction of the nitric oxide-synthesizing pathway in fresh and interleukin 2-cultured rat natural killer cells. 751 50