Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Brazilein (6a,7-dihydro-3,6a,10-trihydroxy-benz[b]indeno[1,2-d]pyran-9(6H)-one) is a compound isolated from Caesalpinia sappan. The vasoactivities of brazilein were evaluated in isolated rat thoracic aorta. The results showed that brazilein can dose-dependently induce contraction of rat thoracic aorta in the resting and phenylephrine pre-evoked state. The average response to 100 microM of brazilein was 30% of the 50 mM KCl contraction, 26% of the 10 muM phenylephrine and 116% of the 20 mM caffeine contraction in comparison. The effects of vasocontraction were proved not to be endothelial dependent and could not be inhibited by alpha-adrenergic receptor blocker phentolamine, beta-adrenergic receptor blocker propranolol, M-adrenaline receptor blocker atropine, angiotensin II receptor blocker losartan or the non-selective nitric oxide synthase (NOS) inhibitor NG-Nitro-L-Arginine Methyl Ester (L-NAME). However the influx of extracellular calcium seemed to be required for this action, because depletion of extracellular calcium and the addition of L-type calcium ion channel antagonist (nimodipine and diltiazem), calcium ion channel activator (BAY-K8644) and potassium ion channel opener (pinacidil) could significantly affect the contraction induced by brazilein. We also investigated the possible signal mechanisms underlying brazilein-induced contraction using selective inhibitors. The inhibitors of myosin light chain kinase (MLCK), Rho-kinase (ROK) and extracellular signal regulated kinase (ERK) can suppress the effect of brazilein respectively, whereas inhibitors of other signaling or receptor molecules such as protein kinase C (PKC) and inositol 1,4,5-triphosphate (IP3) receptor had no effect. All these results demonstrated that brazilein can induce contraction of rat aorta, that the Ca2+ influx, ROK and ERK signal pathways and MLCK activation must be involved in the contractile processes.
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PMID:Brazilein-induced contraction of rat arterial smooth muscle involves activation of Ca2+ entry and ROK, ERK pathways. 1817 58

Carbon monoxide-releasing molecules (CO-RMs) induce nitric oxide (NO) release (which requires NADPH), and Ca2+ -dependent signalling; however, their contribution in mediating endothelial responses to CO-RMs is not clear. Here, we studied the effects of CO liberated from CORM-401 on NO production, calcium signalling and pentose phosphate pathway (PPP) activity in human endothelial cell line (EA.hy926). CORM-401 induced NO production and two types of calcium signalling: a peak-like calcium signal and a gradual increase in cytosolic calcium. CORM-401-induced peak-like calcium signal, originating from endoplasmic reticulum, was reduced by thapsigargin, a SERCA inhibitor, and by dantrolene, a ryanodine receptors (RyR) inhibitor. In contrast, the phospholipase C inhibitor U73122 did not significantly affect peak-like calcium signalling, but a slow and progressive CORM-401-induced increase in cytosolic calcium was dependent on store-operated calcium entrance. CORM-401 augmented coupling of endoplasmic reticulum and plasmalemmal store-operated calcium channels. Interestingly, in the presence of NO synthase inhibitor (l-NAME) CORM-401-induced increases in NO and cytosolic calcium were both abrogated. CORM-401-induced calcium signalling was also inhibited by superoxide dismutase (poly(ethylene glycol)-SOD). Furthermore, CORM-401 accelerated PPP, increased NADPH concentration and decreased the ratio of reduced to oxidized glutathione (GSH/GSSG). Importantly, CORM-401-induced NO increase was inhibited by the PPP inhibitor 6-aminonicotinamide (6-AN), but neither by dantrolene nor by an inhibitor of large-conductance calcium-regulated potassium ion channel (paxilline). The results identify the primary role of CO-induced NO increase in the regulation of endothelial calcium signalling, that may have important consequences in controlling endothelial function.
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PMID:CORM-401 induces calcium signalling, NO increase and activation of pentose phosphate pathway in endothelial cells. 2946 48