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. The increase in the cytosolic Ca(2+) concentration ([Ca(2+)](i)) following repetitive stimulation with ATP or sphingosylphosphorylcholine (SPC) in single porcine aortic smooth muscle cells was investigated using the Ca(2+) indicator, fura-2. 2. The ATP-induced [Ca(2+)](i) increase resulted from both Ca(2+) release and Ca(2+) influx. The former was stimulated by phospholipase C activation, while the latter occurred predominantly via the receptor-operated Ca(2+) channels (ROC), rather than the store-operated Ca(2+) channels (SOC) or the voltage-operated Ca(2+) channel (VOC). Furthermore, the P2X(5) receptor was shown to be responsible for the ATP-induced Ca(2+) influx. 3. A reproducible [Ca(2+)](i) increase was induced by repetitive ATP stimulation, but was abolished by removal of extracellular Ca(2+) or inhibition of intracellular Ca(2+) release using U-73122 or thapsigargin, and was restored by Ca(2+) readdition in the former case. 4. SPC only caused Ca(2+) release, and the amplitude of the repetitive SPC-induced [Ca(2+)](i) increases declined gradually. However, a reproducible [Ca(2+)](i) increase was seen in cells in which protein kinase C being inhibited, which increased the SPC-induced Ca(2+) influx, rather than IP(3) generation. 5. In conclusion, although the amplitude of the ATP-induced Ca(2+) release, measured when Ca(2+) influx was blocked, or of the Ca(2+) influx when Ca(2+) release was blocked, progressively decreased following repetitive stimulation, the overall [Ca(2+)](i) increase for each stimulation under physiological conditions remained the same, suggesting that the Ca(2+) stores were replenished by an influx of Ca(2+) during stimulation. The SPC-induced [Ca(2+)](i) increase resulted solely from Ca(2+) release and decreased gradually following repetitive stimulation, but the decrease could be prevented by stimulating Ca(2+) influx, further supporting involvement of the intracellular Ca(2+) stores in Ca(2+) signalling.
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PMID:Distinct Ca(2+) signalling mechanisms induced by ATP and sphingosylphosphorylcholine in porcine aortic smooth muscle cells. 1074 92

The mechanisms by which bradykinin (BK) increases glucagon release were investigated. BK (0.1-10 microM) increased [Ca(2+)](i) and glucagon release in clonal alpha-cells In-R1-G9. BK-induced glucagon release was lower in the absence than in the presence of extracellular Ca(2+), but it still increased glucagon release while [Ca(2+)](i) was stringently deprived. Depletion of intracellular Ca(2+) store with thapsigargin abolished both the BK-induced Ca(2+) peak and sustained plateau. Microinjection of heparin abolished BK-induced Ca(2+) release. Pertussis toxin (PTX) did not block BK-induced [Ca(2+)](i) increase or glucagon release. U-73122 (8 microM), a phospholipase C (PLC) inhibitor, abolished BK-induced increases in [Ca(2+)](i), but only reduced BK-induced glucagon release by 40%. A phospholipase D (PLD) inhibitor zLYCK reduced BK-induced glucagon release by 60%. The combination of U-73122 and zLYCK abolished BK-induced glucagon release. Both SK&F 96365, a receptor-operated Ca(2+) channel (ROC) blocker and nimodipine, an L-type Ca(2+) channel blocker, reduced BK-induced [Ca(2+)](i) increase and glucagon release. These findings suggest that BK increase glucagon release through a PTX-insensitive G protein and both Ca(2+)-dependent and -independent pathways. The Ca(2+)-dependent pathway is attributable to PLC activation. PLC catalyzes IP(3) formation, inducing Ca(2+) release from the endoplasmic reticulum, which, in turn, triggers Ca(2+) influx via both ROCs and L-type channels. PLD activation may be involved in Ca(2+)-dependent and/or -independent pathway.
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PMID:Mechanisms of bradykinin-induced glucagon release in clonal alpha-cells In-R1-G9: involvement of Ca(2+)-dependent and -independent pathways. 1208 64

Although lysophosphatidic acid (LPA) is known to increase intracellularfree calcium concentration ([Ca(2+)](i)) in different cell types, the effect of LPA on the skeletal muscle cells is not known. The present study was therefore undertaken to examine the effect of LPA on the [Ca(2+)](i) in C2C12 cells. LPA induced a concentration and time dependent increase in [Ca(2+)](i), which was inhibited by VPC12249, VPC 32183 and dioctanoyl glycerol pyrophosphate, LPA1/3 receptor antagonists. Pertussis toxin, a G(i) protein inhibitor, also inhibited the LPA-induced increase in [Ca(2+)](i). Inhibition of tyrosine kinase activities with tyrphostin A9 and genistein also prevented the increase in [Ca(2+)](i) due to LPA. Likewise, wortmannin and LY 294002, phosphatidylinositol 3-kinase (PI3-K) inhibitors, inhibited [Ca(2+)](i) response to LPA. The LPA effect was also attenuated by ethylene glycolbis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA), an extracellular Ca(2+) chelator, Ni(2+) and KB-R7943, inhibitors of the Na(+)-Ca(2+) exchanger; the receptor operated Ca(2+) channel (ROC) blockers, 2-aminoethoxydiphenyl borate and SK&F 96365. However, the L-type Ca(2+) channel blockers, verapamil and diltiazem; the store operated Ca(2+) channel blockers, La(3+) and Gd(3+); a sarcoplasmic reticulum calcium pump inhibitor, thapsigargin; an inositol trisphosphate receptor antagonist, xestospongin and a phospholipase C inhibitor, U73122, did not prevent the increase [Ca(2+)](i) due to LPA. Our data suggest that the LPA-induced increase in [Ca(2+)](i) might occur through G(i)-protein coupled LPA(1/3) receptors that may be linked to tyrosine kinase and PI3-K, and may also involve the Na(+)-Ca(2+) exchanger as well as the ROC. In addition, LPA stimulated C2C12 cell proliferation via PI3-K. Thus, LPA may be an important phospholipid in the regulation of [Ca(2+)](i) and growth of skeletal muscle cells.
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PMID:Mechanisms of the lysophosphatidic acid-induced increase in [Ca(2+)](i) in skeletal muscle cells. 1849 35