Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0018099 (
gout
)
5,192
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Recently, attention has focused on the effects of weather conditions and seasonal changes on the incidence of acute microcrystalline events. Acute
gout
attacks are more frequent during the spring, but seasonal variations in the incidence of acute pseudogout attacks are less clearly defined. Genetic analysis of two unrelated families with calcium pyrophosphate dihydrate (CPPD) crystal deposition disease showed linkage to the short arm of chromosome 5p. Several recent reports show CPPD crystal disease occurring in association with Gitelman syndrome, the hypocalciuric-hypomagnesemic variant of Bartter syndrome. Two signaling pathways, protein kinase C and
adenyl cyclase
, modulate generation of extracellular pyrophosphate by porcine cartilage chrondrocytes. These transduction mechanisms may provide potential targets for the treatment of CPPD crystal deposition disease. A controlled clinical trial showed ultrasound therapy to be beneficial in the treatment of symptomatic chronic calcific tendinitis of the shoulder. There is evidence that apatite crystals may contribute to cartilage damage in osteoarthritis and that therapeutic interventions to prevent the formation and biologic effects of the crystals may potentially retard the progression of the osteoarthritic process.
...
PMID:What is new about crystals other than monosodium urate? 1080 54
In isolated leukocytes, elevation of cAMP can inhibit various proinflammatory and immune functions. The prostaglandins E (PGEs) are known to stimulate leukocyte cAMP production, and for years they have been viewed as potential immunosuppressive and/or anti-inflammatory agents. However, their clinical use is severely limited by extreme metabolic instability and by poor oral absorption, which necessitates administration by infusion or injection. Misoprostol is a synthetic analog of PGE(1) that is relatively stable and orally absorbable. We examined the effects of misoprostol on cAMP production in leukocytes, in view of the possibility that it mimics PGE(1) and, thus, might represent a clinically useful immunosuppresive or anti-inflammatory drug. Our results indicate the following: (1) Misoprostol increases leukocyte cAMP production in a dose-dependent manner (similar20 nM to >100 &mgr;M) and acts by stimulating
adenylate cyclase
. (2) Its potency and maximal effect are somewhat less than those of PGE(1) (3) cAMP generation in response to either misoprostol or PGE(1) is transient (in the presence of isobutylmethylxanthine to inhibit endogenous phosphodiesterases). (4) Misoprostol's stimulation of
adenylate cyclase
is synergistically increased by pretreatment of cells with colchicine, a microtubule-disrupting agent that is currently used for prophylaxis and treatment of
gout
. (5) Colchicine acts by increasing the initial rate of cAMP production and not by prolonging the response to misoprostol. (6) A clinically relevant dose of colchicine (0.25 &mgr;M) is effective given sufficient pretreatment time. (7) Whereas a clinically relevant dose of misoprostol (3 nM) is ineffective alone, preexposure of cells to colchicine enables such a dose to stimulate cAMP generation significantly. The combination of misoprostol with colchicine might eventually prove useful in the therapy of immune or inflammatory disease.
...
PMID:Misoprostol Stimulates cAMP Generation in Human Leukocytes: Synergy with Colchicine Suggests a New Potential for Established Drugs. 1185 51
Nod-like receptor protein 3 (NLRP3)-mediated pyroptosis has a causal role in the pathogenesis of
gout
. P2Y
14
receptor (P2Y
14
R) distributed in immune cells including macrophages is a Gi-coupled receptor that inhibits the synthesis of cAMP, which has been regarded as a potential regulator of inflammatory response. Nevertheless, the role of P2Y
14
R in MSU-induced pyroptosis of macrophages involved in acute gouty arthritis is still unclear. In our present study, P2Y
14
R knockout (P2Y
14
R-KO) disrupted MSU-induced histopathologic changes in rat synoviums, accompanied with a significant inhibition of pyroptotic cell death characterized by Caspase-1/PI double-positive and blockade of NLRP3 inflammasome activation in synovial tissues, which was consistent with that observed in in vitro studies. Owing to the interaction of NLRP3 inflammasome and cAMP, we then investigated the effect of
adenylate cyclase
activator (Forskolin) on macrophage pyroptosis and
gout
flare caused by MSU stimulation. The reversal effect of Forskolin verified the negative regulatory role of cAMP in MSU-induced pyroptosis. More importantly,
adenylate cyclase
inhibitor (SQ22536) intervention led to a reversal of protection attributed to P2Y
14
R deficiency. Findings in air pouch animal models also verified aforementioned experimental results. Our study first identified the role of P2Y
14
R/cAMP/NLRP3 signaling pathway in acute gouty arthritis, which provides a novel insight into the pathological mechanisms of pyroptosis-related diseases.
...
PMID:P2Y
14
receptor has a critical role in acute gouty arthritis by regulating pyroptosis of macrophages. 3245 91
