Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Cultured brain capillary endothelial cells of the rat respond to endothelin-1 (ET-1) by an increased activity of the Na+,K+,2Cl-, cotransporter and a mobilization of intracellular Ca2+ stores. 2. Calyculin A (1-30 nM), but not okadaic acid, sensitizes up to 100 fold the Na+,K+,2Cl- cotransporter to the action of ET-1. 3. Calyculin A (30 nM) does not modify the binding properties of ET-1 to ETA receptors. 4. Calyculin A (30 nM) inhibits ET-1 induced intracellular Ca2+ mobilization. 5. It is concluded that inhibition of protein phosphatase 1 selectively modifies the repertoire of intracellular actions of ET-1 and favours actions that are unrelated to the phospholipase C signalling cascade.
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PMID:Sensitization by calyculin A of brain capillary endothelial cells to endothelin-1. 778 Jun 34

Cholinergic agents regulate proximal tubule acidification but the mechanism responsible for this effect is unclear. We examined the effect of the cholinergic agent carbachol on the activity of the Na-HCO3 cotransporter in primary cultures of the proximal tubule of the rabbit. The activity of the cotransporter was assayed either as HCO3-dependent 22Na uptake or as the recovery of intracellular pH in cells perfused continuously with Cl-free physiologic solution containing amiloride to block the Na-H antiporter. Carbachol caused a dose-dependent stimulation of the cotransporter activity with a maximum increase of 90% above control values at 10(-5) M and half maximal stimulation at 10(-7) M. The stimulation was blocked by atropine and pirenzepine indicating an effect through the M1 muscarinic receptor. Carbachol increased intracellular calcium fourfold and the rise in cytosolic calcium was prevented by the intracellular calcium chelator, BAPTA. BAPTA also blocked the effect of carbachol on the cotransporter. Because carbachol activates phospholipase C and protein kinase C, we examined the effect of carbachol in the presence of the phospholipase C inhibitor, U73122, or the PKC inhibitor, calphostin C, or PKC depletion. The phospholipase C inhibitor prevented both the effect of carbachol on the cotransporter and on the intracellular Ca. Calphostin C and PKC depletion also prevented the stimulation of the cotransporter. Carbachol increased PKC activity and caused translocation of the PKC to the particulate fraction. We also examined the effect of the phosphatase inhibitor, calyculin A or the calmodulin kinase inhibitor, W-13 on carbachol stimulation. Calyculin A and W13 likewise prevented the carbachol-induced stimulation of the cotransporter. These results demonstrate that cholinergic stimulation modulated the activity of the cotransporter through multiple pathways including phospholipase C/PKC and phosphatase systems.
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PMID:Regulation of the renal Na-HCO3 cotransporter: VII. Mechanism of the cholinergic stimulation. 908 72

The signal transduction pathways that trigger dephosphorylation of cofilin in neutrophils stimulated with the chemoattractant fMet-Leu-Phe (fMLP) were investigated with a phospho-specific antibody that recognized cofilin only when this protein was phosphorylated on ser-3. Unlike earlier studies that monitored changes in (32)P-labeled cofilin, this Ab allowed us to monitor changes in the total mass of phosphorylated cofilin during neutrophil stimulation. Neutrophils stimulated with fMLP (1.0 microM) for 1.0 min exhibited a massive loss (> 85%) of phosphate from cofilin, which was blocked by an antagonist of phosphoinositide-specific phospholipase C (PI-PLC) (1.0 microM U73122). Products of PI-PLC, sn-1,2-diglyceride and inositol (1,4,5)-trisphosphate, are known to activate protein kinase C (PKC) and increase intracellular Ca(2+), respectively. Treatment of neutrophils with agents that selectively activate PKC [4beta-phorbol 12-myristate 13-acetate (PMA) ] or cellular Ca(2+) (ionophore A23187) also triggered dephosphorylation of cofilin. Both a nonspecific (100 nM staurosporine) and a highly selective antagonist of PKC (200 nM bisindolylmaleimide I) blocked dephosphorylation of cofilin in neutrophils stimulated with PMA but not with fMLP or ionophore A23187. The calmodulin (CaM) antagonists trifluoperazine (15 microM) and W-7 (50 microM) blocked dephosphorylation of cofilin in stimulated neutrophils whereas inactive/less-active analogs of these inhibitors (15 microM promethazine, 50 microM W-5) were substantially less effective. Calyculin A (40 nM), an antagonist of type 1 and 2A protein phosphatases, also triggered a massive dephosphorylation of cofilin in unstimulated neutrophils through a pathway that was insensitive to inhibitors of type 2B phosphatases. These data suggest that both PKC-dependent and independent pathways can trigger dephosphorylation of cofilin in neutrophils with the latter pathway predominating in fMLP-stimulated cells. These pathways may also contain CaM and a type 2C and/or novel phosphatase (e.g., slingshot).
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PMID:Products of phosphoinositide specific phospholipase C can trigger dephosphorylation of cofilin in chemoattractant stimulated neutrophils. 1245 91