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)

Changes in contractile force were measured during isometric contraction of the bovine middle cerebral artery caused by stimulation of various receptors and by application of high K+, caffeine, and protein kinase C (PKC)-activators. The protein tyrosine kinase (PTK)-inhibitors, such as genistein and tyrphostin, were applied before testing the effect on the contractions or during the maximal plateau of the contraction. The contractions induced by serotonin, prostaglandin F2 alpha, endothelin-1, and thromboxane A2 were significantly and dose-dependently depressed by the PTK-inhibitors (IC50 2-15 microM). In contrast, contractions were significantly augmented by 1 microM pervanadate, an inhibitor of phosphoprotein tyrosine phosphatase. Lineweaver-Burk plotting of the dose-response curves with an increase in inhibitor concentration indicated that the receptor affinity for each agonist remained unchanged in spite of marked depression of the responses. Although the effect was not significant, contractions induced by both high K+ and caffeine were also depressed slightly by PTK-inhibitors in the same range of concentrations used for receptor-induced contractions. Contractions induced by PKC-activators, such as 1-oleoyl-2-acetyl-sn-glycerol and phorbol-12,13-diacetate, were significantly depressed by PTK-inhibitors at concentrations similar to those used for receptor-induced contractions. The results suggest that receptor stimulations which produce sequential activation of phospholipase C and PKC can activate PTK and trigger the so-called "PTK-cascade" causing a sustained or long-lasting contraction similar to the cerebral vasospasm observed clinically.
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PMID:Modulatory role of protein tyrosine kinase activation in the receptor-induced contractions of the bovine cerebral artery. 955 33

Cerebral vasospasm determines the prognosis of subarachnoid hemorrhage (SAH). The increased vascular reactiveness has an important role in the development of cerebral vasospasm. This study analyzed the roles of the receptor-mediated signaling and the myofilament Ca(2+) sensitivity in the increased vascular reactiveness in SAH, using the basilar artery of a rabbit SAH model. Endothelin-1, thrombin, and phenylephrine induced transient increases in [Ca(2+)](i), myosin light chain phosphorylation, and contraction in the controls. All these responses were not only enhanced but also became sustained in SAH. In the sequential stimulation of thrombin receptor or alpha(1)-adrenoceptor, the second response was substantially attenuated in the controls, whereas it was maintained in SAH. The thrombin-induced contraction in SAH irreversibly persisted even after terminating the thrombin stimulation. This contraction was completely reversed by trypsin and a Galpha(q) inhibitor YM254890, thus suggesting the sustained receptor activity during the sustained contraction. YM254890 also inhibited the endothelin-1- and phenylephrine-induced sustained contraction. Furthermore, the GTPgammaS-induced transient contraction in the control alpha-toxin-permeabilized strips was converted to a sustained contraction in SAH. The results provide the first evidence that the feedback inactivation of the receptor activity and the myofilament Ca(2+) sensitivity was impaired in SAH, thus contributing to the increased vascular reactiveness.
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PMID:Impaired feedback regulation of the receptor activity and the myofilament Ca2+ sensitivity contributes to increased vascular reactiveness after subarachnoid hemorrhage. 2023 81

Neuron apoptosis and inflammatory responses contribute to subarachnoid hemorrhage (SAH)-induced early brain injury (EBI), which is the main aspect that affects patients' outcome. Previous research has demonstrated that phosphatidylcholine-specific phospholipase C (PC-PLC) plays critical roles in cell apoptosis and various inflammatory responses, and that tricyclodecan-9-yl-xanthogenate (D609), a well known PC-PLC inhibitor, is a powerful agent to protect brain from cerebral ischemic injury and SAH-induced cerebral vasospasm. However, the association between PC-PLC and SAH-induced EBI is undetermined. Therefore, we sought to investigate whether PC-PLC was implicated in SAH-induced EBI. Compared with sham group, an upregulation of PC-PLC activity was detected in the brain tissue and serum of SAH group. Pharmacological blockade of PC-PLC by D609 attenuated neurological behavior impairment, brain edema and blood-brain barrier (BBB) damage induced by SAH. In addition, D609 treatment significantly inhibited SAH-induced inflammatory response and neuron apoptosis. Furthermore, inhibition of PC-PLC in primary-cultured rat cortical neurons attenuated oxyhemoglobin (OxyHb)-induced apoptosis morphology and decrease in survival rate. In conclusion, our data suggest that PC-PLC participates in SAH-induced EBI.
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PMID:Evidence for the role of phosphatidylcholine-specific phospholipase in experimental subarachnoid hemorrhage in rats. 2574 18