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)

Interferon-alpha (IFN-alpha) and transforming growth factor-beta 1 (TGF-beta 1) have been reported in different brain regions. The amygdala contains high levels of corticotropin releasing factor (CRF) and has been implicated as a central site for its stress-related autonomic and behavioral response. IFN-alpha will release arginine vasopressin (AVP) from both amygdala and hypothalamus, which further supports a role for the amygdala in neuroimmune interactions. In the present study, we compared the effects of these cytokines on the in vitro release of CRF from the amygdala and hypothalamus. In addition, we evaluated the possible involvement of guanylate cyclase-mediated signaling in CRF release. IFN-alpha stimulates CRF release from both amygdala and hypothalamus. The CRF release by IFN-alpha, Interleukin-2 (IL-2) and acetylcholine is blocked by guanylate cyclase inhibitors, indicating a role for cGMP accumulation in this CRF release. TGF-beta 1 had no effect on basal release of CRF, nor on the CRF-release induced by IL-2, but selectively blocked the acetylcholine-induced release in both amygdala and hypothalamus. Taken with a previous report that TGF-beta 1 specifically inhibits AVP release by acetylcholine, these results suggest that TGF-beta 1 may modulate HPA axis activation, by antagonizing (acetylcholine-evoked) CRF and AVP release. These data further support a role for the amygdala in the bidirectional communication between neuroendocrine and immune system.
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PMID:Interferon-alpha and transforming growth factor-beta 1 regulate corticotropin-releasing factor release from the amygdala: comparison with the hypothalamic response. 910 61

Interleukin-2 (IL-2) therapy often results in potentially life-threatening side effects including hypotension. However, the mechanism has not been completely elucidated. In order to determine whether IL-2 modifies vascular tone, we investigated the effect of IL-2 on rat thoracic aorta rings and the underlying mechanisms. Effects of IL-2 on the contraction of high KCl and phenylephrine (PE) preconstricted rat thoracic aorta with or without endothelium were determined by organ bath technique. To explore the mechanism, nitric oxide synthase inhibitor L-N(G)-nitroarginine methyl ester (L-NAME), guanylyl cyclase inhibitor methylene blue, and cyclooxygenase inhibitor indomethacin were used. IL-2 (10-1000 U/ml) caused concentration-dependent relaxation of aorta rings preconstricted with PE (10 micromol/L) in endothelium-intact rings, but had no effect on KCl (120 mmol/L) preconstricted rings. Removal of the endothelium, or pretreatment with L-NAME (0.1 mmol/L) or methylene blue (10 micromol/L) or indomethacin (10 micromol/L), inhibited the relaxation of IL-2. The results indicate that the relaxation by IL-2 in rat aorta ring is endothelium-dependent and is possibly mediated by the NO-guanylyl cyclase pathway and cyclooxygenase-dependent pathway.
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PMID:[Interleukin-2 induced endothelium-dependent relaxation of rat thoracic aorta]. 1259 29