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Query: EC:3.1.4.3 (
phospholipase C
)
18,461
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Ventral regions of the medulla oblongata of the brainstem are populated by astrocytes sensitive to physiological changes in P
CO2
/[H
+
]. These astrocytes respond to decreases in pH with elevations in intracellular Ca
2+
and facilitated exocytosis of ATP-containing vesicles. Released ATP propagates Ca
2+
excitation among neighboring astrocytes and activates neurons of the brainstem respiratory network triggering adaptive increases in breathing. The mechanisms linking increases in extracellular and/or intracellular P
CO2
/[H
+
] with Ca
2+
responses in chemosensitive astrocytes remain unknown. Fluorescent imaging of changes in [Na
+
]
i
and/or [Ca
2+
]
i
in individual astrocytes was performed in organotypic brainstem slice cultures and acute brainstem slices of adult rats. It was found that astroglial [Ca
2+
]
i
responses triggered by decreases in pH are preceded by Na
+
entry, markedly reduced by inhibition of Na
+
/HCO
3
-
cotransport (NBC) or Na
+
/Ca
2+
exchange (NCX), and abolished in Na
+
-free medium or by combined NBC/NCX blockade. Acidification-induced [Ca
2+
]
i
responses were also dramatically reduced in brainstem astrocytes of mice deficient in the electrogenic Na
+
/HCO
3
-
cotransporter NBCe1. Sensitivity of astrocytes to changes in pH was not affected by inhibition of Na
+
/H
+
exchange or blockade of
phospholipase C
. These results suggest that in pH-sensitive astrocytes, acidification activates NBCe1, which brings Na
+
inside the cell. Raising [Na
+
]
i
activates NCX to operate in a reverse mode, leading to Ca
2+
entry followed by activation of downstream signaling pathways. Coupled NBC and NCX activities are, therefore, suggested to be responsible for functional CO
2
/H
+
sensitivity of astrocytes that contribute to homeostatic regulation of brain parenchymal pH and control of breathing.
...
PMID:Mechanisms of CO2/H+ Sensitivity of Astrocytes. 2779 30
Carbon monoxide
-releasing molecules (CO-RMs) induce nitric oxide (NO) release (which requires NADPH), and Ca
2+
-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.
...
PMID:CORM-401 induces calcium signalling, NO increase and activation of pentose phosphate pathway in endothelial cells. 2946 48
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