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)

1. Experiments were performed to investigate the effects of human recombinant interleukin-1 beta on the production of vasoactive substances by human aortic smooth muscle cells in culture. Smooth muscle cells were cultured either on microcarrier beads for bioassay experiments, or in multiwell plates for the determination of nitrite levels. 2. Cells were grown on microcarrier beads, treated with interleukin-1 beta or vehicle (control) for 24 h, and packed in a column which was perfused with oxygenated Krebs-Ringer solution in the presence of indomethacin. The activity of the perfusates was bioassayed by measuring the changes in tension of a contracted ring of Wistar rat aorta without endothelium, and by evaluating the modulation of thrombin-induced platelet aggregation. 3. Perfusates from interleukin-1 beta treated cells evoked relaxations of the contracted detector tissues, and microcarrier beads covered with treated cells inhibited thrombin-induced platelet aggregation. Superoxide dismutase enhanced these effects whereas Methylene Blue abolished them. Control cells evoke neither relaxation nor inhibition of platelet aggregation. Interleukin-1 beta induced a time- and concentration-dependent production of nitrite. Cycloheximide and nitro-L-arginine inhibited the relaxations and the production of nitrite evoked by interleukin-1 beta-treated cells. L-Arginine but not D-arginine overcame the blockade elicited by nitro-L-arginine. Transforming growth factor-beta 1 reduced the interleukin-1 beta-dependent generation of nitrite by cultured smooth muscle cells and relaxation of contracted bioassay tissues. 4. Interleukin-1 beta, transforming growth factor-beta 1, Methylene Blue and L-arginine-related compounds did not induce significant variations of tension of the detector rings. 5. These data demonstrate that the inflammatory and immunological mediator interleukin-1 can stimulate the production of a nitric oxide-like substance(s) in cultured human smooth muscle cells leading to the activation of soluble guanylate cyclase. Liberation of transforming growth factor-beta by activated platelets may inhibit these reactions.
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PMID:Inhibition of cytokine-induced nitric oxide production by transforming growth factor-beta 1 in human smooth muscle cells. 128 59

Interferon-alpha and transforming growth factor-beta 1 have been detected in the brain, suggesting their possible regulatory functions. In the present study, we evaluated the effects of these cytokines on the in vitro release of arginine vasopressin, previously reported to be sensitive to neurotransmitters such as acetylcholine, norepinephrine, and corticotropin releasing hormone as well as to cytokines interleukin-1 and interleukin-2. Interferon-alpha was found to enhance arginine vasopressin release from both hypothalamus and amygdala, as was dibutyryl cyclic GMP. Blockade of nitric oxide synthase antagonized the interferon-alpha induced arginine vasopressin release from the amygdala but not from the hypothalamus. Transforming growth factor-beta 1 had no effect on basal release of arginine vasopressin, nor on the arginine vasopressin-release induced by interferon-alpha, interleukin-2 or norepinephrine, but selectively blocked the acetylcholine-induced release in both hypothalamus and amygdala. When the release of arginine vasopressin induced by interferon-alpha, interleukin-2, acetylcholine and norepinephrine was probed with inhibitors of guanylate cyclase, the interactions exhibited regional selectivity: neither the interleukin-2-induced arginine vasopressin release from hypothalamus, nor the norepinephrine-induced release of arginine vasopressin from either amygdala or hypothalamus was affected by guanylate cyclase inhibitors, but all other arginine vasopressin releasers were blocked. Taken with previous reports that interferon-alpha will enhance hypothalamic corticotropin releasing hormone release, our results suggest that arginine vasopressin release enhanced by interferon-alpha may also contribute to the activation of the hypothalamic-pituitary axis, while the ability of transforming growth factor-beta 1 to diminish the arginine vasopressin released by acetylcholine could mediate some of this cytokine's central effects. The extension of these neurotransmitter-cytokine interactions to the amygdala may provide an additional basis for interactions between neuronal and immune systems.
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PMID:Arginine vasopressin release by acetylcholine or norepinephrine: region-specific and cytokine-specific regulation. 886 47