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)

The vasoconstrictor effect, the binding, and the response of inositol phosphates to endothelin-1 (ET-1) were investigated in blood vessels of deoxycorticosterone acetate (DOCA)-salt hypertensive rats within 2 weeks of development of hypertension and in uninephrectomized control rats. In DOCA-salt and uninephrectomized rats, plasma levels of endothelin were similar (1.2 +/- 0.1 fmol/ml). Thoracic aorta and mesenteric artery rings devoid of endothelium presented significantly decreased responses to increasing concentrations of ET-1. Binding of ET-1 to mesenteric artery membranes was significantly lower in DOCA-salt rats (106 +/- 22 fmol/mg protein) than in uninephrectomized rats (172 +/- 19 fmol/mg protein, p less than 0.05), whereas affinity was similar. Phosphoinositide metabolism was examined in aorta and mesenteric arteries after incubation with [3H]myoinositol. Inositol phosphates were separated by high-performance liquid chromatography. In response to 100 nmol/l ET-1, accumulation of inositol 1,4,5-trisphosphate after 20 seconds and of inositol monophosphate, inositol bisphosphate, and inositol 1,3,4-triphosphate after 30 minutes (in the presence of 25 mmol/l LiCl) were significantly lower in DOCA-salt hypertensive than in uninephrectomized control rats, in both aorta and mesenteric arteries. In conclusion, decreased density of ET-1 receptors in DOCA-salt hypertensive rats results in decreased activation of phospholipase C and, consequently, reduced vasoconstriction induced by ET-1. Because the decrease in vasoconstrictor effects of ET-1 is found in the absence of endothelium, it is likely that receptor downregulation rather than prior receptor occupancy underlies these findings.
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PMID:Endothelin vascular receptors and responses in deoxycorticosterone acetate-salt hypertensive rats. 131 Apr 86

Recent studies suggest that serotonergic receptor activation is coupled to phospholipase C-mediated phosphoinositide hydrolysis, which results in the release of intracellular second messengers. The purpose of this study was to determine whether altered phosphoinositide metabolism is the basis for augmented vascular responsiveness to serotonin in genetic hypertension. Thoracic aortic segments isolated from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto normotensive rats (WKY) were labeled with myo-[3H]inositol and stimulated with serotonin in the presence of LiCl. Accumulation of [3H]inositol phosphates was then quantitated by column chromatography. Basal inositol phosphate accumulation and basal incorporation of myo-[3H]inositol into aortic cell membranes from SHRSP was not significantly different from WKY values. At 2.6 x 10(-7) to 2.6 x 10(-4) M serotonin, phosphoinositide metabolism was significantly augmented in aortae from SHRSP compared with WKY. Depolarization (100 mM KCl) did not increase phosphoinositide hydrolysis above basal levels in SHRSP or WKY. 2-Nitro-4-carboxyphenyl-N,N-diphenyl carbamate (NCDC), an inhibitor of phospholipase C, prevented the serotonin-induced phosphoinositide metabolism. NCDC also partially inhibited phasic contractions (responses in calcium-free solution) to serotonin in aortas from SHRSP and WKY. In conclusion, abnormal phosphoinositide metabolism may be one mechanism responsible for the characteristic increase in vascular reactivity to serotonin in hypertension.
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PMID:Augmented phosphoinositide metabolism in aortas from genetically hypertensive rats. 215 30

Deoxycorticosterone-salt (DOCA-salt) hypertension is characterized by elevated vasoconstriction to agonists that stimulate G protein-mediated activation of phospholipase C. However, the mechanisms responsible for the augmented responsiveness are unknown. This study tested the hypothesis that this augmented vascular responsiveness is due to elevated content of G(alpha)q, the G protein alpha-subunit that activates phospholipase C. Thoracic aortae from DOCA-salt hypertensive rats (systolic blood pressure 183 +/- 7 mm Hg) and normotensive controls (systolic blood pressure 115 +/- 2 mm Hg) were homogenized and G protein content determined. Western analysis revealed that G(alpha)i content was decreased in DOCA compared with control rats (1364 +/- 196 versus 2343 +/- 188 densitometry units, P < or = .05) with no differences observed for G(alpha)q or G(alpha)s. In addition, contractile responses in denuded femoral artery strips revealed a significant decrease in EC50 values in DOCA arteries to all of the agonists examined: aluminum fluoride (DOCA = 1.42, control = 2.34 mmol/L), mastoparan (DOCA = 0.51, control = 35 micromol/L), phenylephrine (DOCA = 0.08, control = 0.53 micromol/L), and serotonin (DOCA = 0.014, control = 0.04 micromol/L, EC20 values). Finally, arteries from DOCA rats contracted with aluminum fluoride had increased sensitivity to G protein antagonists but not to a phospholipase C inhibitor. The enhanced contractile responsiveness in the DOCA arteries may be mediated in part through decreased G(alpha)i levels. However, it is not caused by increased concentrations of G(alpha)q in the cell membrane or by increased phospholipase C sensitivity, and the increased constrictor response to G protein stimulators of phospholipase C appears to depend primarily on increased G protein sensitivity.
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PMID:Increased responsiveness and decreased expression of G proteins in deoxycorticosterone hypertension. 861 34