Inositol Trisphosphate and Diacylglycerol: Two Interacting Second Messengers

Berridge, Michael J.

doi:10.1146/annurev.bi.56.070187.001111

Cited by 3,261 publications

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References 138 publications

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“…It has been established that DAG, together with IP3, is generated from the phosphatidylinositol (PI) cycle upon receptor stimulation (Berridge, 1987). Generally, the activation of the PI cycle upon re ceptor stimulation is only transient.…”

Section: Discussionmentioning

confidence: 99%

Possible Role of Protein Kinase C-Dependent Smooth Muscle Contraction in the Pathogenesis of Chronic Cerebral Vasospasm

Matsui¹,

Takuwa

Johshita³

et al. 1991

J Cereb Blood Flow Metab

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Summary:In the present study, we investigate the pos sible role of protein kinase C (PKC)-dependent smooth muscle contraction in cerebral vasospasm following sub arachnoid hemorrhage (SAH), employing the beagle "two-hemorrhage" model. The occurrence of chronic va sospasm was angiographically confirmed on day 7 in the basilar artery, which was exposed via the transclival ap proach. The artery was superfused with aerated Krebs Henseleit solution containing various agents, and the sub sequent changes in the basilar artery diameter were re corded by successive angiography. The preexisting spasm was not ameliorated by local application of neuro transmitter antagonists (atropine, methysergide, phentol amine, and diphenhydramine), calmodulin inhibitors (R24571 and W-7), or a calcium antagonist, nicardipine. However, the application of PKC inhibitors such as H-7 and staurosporine induced significant dilation of the ar tery. In another experiment, an intrinsic PKC activator,The refractoriness of chronic vasospasm to va sodilator therapy has been well documented (Bevan and Bevan, 1988). Particularly, the Ca2+ -antagonist nimodipine, administered via various routes, has in variably failed to reverse chronic vasospasm (Espi nosa et aI. , 1984; Grotenhuis et aI., 1984; Nosko et aI., 1985; Lewis et aI., 1988). Since agonist-induced smooth muscle contraction has been thought to be dependent on intracellular influx of external Ca2+, Received December 28, 1989; revised July 23, 1990; accepted July 24, 1990. 1431,2-diacylglycerol (DAG), in the basilar artery, the CSF, and the cisternal clot of beagles exposed to two hemor rhages was measured on days 1, 2,4,7, and 14 using the DAG kinase method. On days 2, 4, and 7, the DAG con tent of the basilar artery showed a significant and pro longed increase (150-190% of control), whereas it was unchanged on days I and 14. Throughout the experimen tal period, there was a significant linear correlation be tween the DAG content and the angiographical diameter of the basilar artery. The above results indicate that SAH leads to an increase in the DAG level within the cerebral artery through an as yet unknown mechanism and that subsequent activation of the PKC-dependent contractile system participates in the occurrence of chronic vaso spasm. Key Words: Cerebral vasospasm-l,2-Diac ylglycerol-H-7-Protein kinase C-Vascular smooth muscle.it has been conjectured that the primary cause of chronic vasospasm might be the changes in the physical properties in the arterial wall rather than active smooth muscle contraction (Bevan and Be van, 1988; Findlay et aI., 1989; Kim et aI., 1989).However, it has recently been shown that during the sustained phase of agonist-induced smooth mus cle contraction, neither the intracellular concentra tion of Ca2+ nor the phosphorylation of myosin light chain is increased (DeFeo and Morgan, 1985;Kamm and Stull, 1985). To explain the force main tenance during the sustained phase of smooth mus cle contraction, the occurrence of a "latch mechanism" in the myosin-actin i...

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Section: Discussionmentioning

confidence: 99%

Possible Role of Protein Kinase C-Dependent Smooth Muscle Contraction in the Pathogenesis of Chronic Cerebral Vasospasm

Matsui¹,

Takuwa

Johshita³

et al. 1991

J Cereb Blood Flow Metab

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“…The stimulation of neutrophils by receptor-binding ligands can activate phospholipase C (PLC) with the formation of inositol trisphosphate, which increases in [Ca 2 ] i , and diacylglycerol, which activates PKC [42]. We next investigated the role of PLC/Ca 2 on ERK activation.…”

Section: Plc/ca 2 Pathway Couples To the Activation Of Erkmentioning

confidence: 99%

Examination of the signal transduction pathways leading to activation of extracellular signal‐regulated kinase by formyl‐methionyl‐leucyl‐phenylalanine in rat neutrophils

Chang

Wang

1999

FEBS Letters

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The signaling pathways leading to extracellular signal-regulated kinase (ERK) activation in formyl-methionylleucyl-phenylalanine (fMLP)-stimulated rat neutrophils were examined. fMLP-stimulated ERK activation based on immunoblot analysis with antibodies against the phosphorylation form of ERK was attenuated by the pretreatment of cells with pertussis toxin but not with a dual cyclo-oxygenase/lipoxygenase inhibitor BW755C. Exposure of cells to the tyrosine kinase inhibitor genistein, phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and LY294002, or protein kinase C (PKC) inhibitors Go «6976, Go «6983, and GF109203X inhibited fMLP-stimulated ERK phosphorylation in a concentration-dependent manner. In addition, both the phospholipase C (PLC) inhibitor U73122 and the Ca 2 chelator BAPTA attenuated ERK activation. These results indicate that G iao protein, tyrosine kinase, PI3K, PKC, and PLC/Ca 2 , but not arachidonate metabolites, act upstream of fMLP-stimulated ERK activation.z 1999 Federation of European Biochemical Societies.

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“…Hormone-induced second messengers such as Ins(l,4,5)P, were shown to release Ca2", presumably from endo(sarco)plasmic reticulum (Berridge, 1987) or 'calciosome' pools (Volpe et al, 1988). In this respect the properties of the cellular Ca"2 buffers and of the Ca2+-transporting systems are of prime interest.…”

Section: Polyamines and Transportmentioning

confidence: 99%

“…Polyamines and polyphosphoinositide metabolism Polyamines have been shown to affect the formation and the metabolism of diacylglycerol and Ins(1,4,5)P3, which are generated by a Ca2"-dependent phosphoinositide-specific phospholipase C-catalysed hydrolysis of Ptdlns(4,5)P2, a phospholipid located in the inner monolayer of plasma membranes. These intracellular second messengers belong to the major pathway of signal transduction during the response of cells to external receptor ligands (for a review see Berridge, 1987). Diacylglycerol is an endogenous activator, at the plasma membrane level, of protein kinase C, whereas Ins(1,4,5)P3, which diffuses through the cytoplasm, causes the release of Ca2+ from nonmitochondrial intracellular stores.…”

Section: Polyamines and Transportmentioning

confidence: 99%