Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

Neuropeptide Y (NPY) significantly potentiates the constrictor actions of noradrenaline and ATP on blood vessels via a pertussis toxin (PTX)-sensitive mechanism involving Gi/o (alpha beta gamma) protein subunits (Gi/o, GTP-binding proteins sensitive to PTX). In Chinese hamster ovary K1 (CHO K1) cells expressing specific receptors for these neurotransmitters, stimulation of Gi/o protein-coupled receptors for NPY and other neurotransmitters can augment the Gq/11-coupled (Gq/11, GTP-binding proteins insensitive to PTX) alpha 1B adrenoceptor- or ATP receptor-induced arachidonic acid (AA) release and inositol phosphate (IP) production (early events which may precede vasoconstriction). In this study, we have assessed the role of G beta gamma subunits in the synergistic interaction between Gi/o- (NPY Y1, 5-hydroxytryptamine 5-HT1B, adenosine A1) and Gq/11- [ATP P2Y2 (P2U)]-coupled receptors on AA release by using the specific abilities of regions of the beta-adrenergic receptor kinase (beta ARK1 residues 495-689) and the transducin alpha subunit to associate with G-protein beta gamma subunit dimers and to act as G beta gamma subunit scavengers. Transient expression of beta ARK1(495-689) in CHO K1 cells heterologously expressing NPY Y1 receptors had no significant effect on the PTX-insensitive ability of ATP to stimulate AA release. Stimulation of NPY Y1 receptors (as well as the endogenous 5-hydroxytryptamine 5-HT1B receptor and the transiently expressed human adenosine A1 receptor) resulted in a PTX-sensitive augmentation of ATP-stimulated AA release, which was inhibited by expression of both G beta gamma subunit scavengers. Expression of beta ARK1(495-689) similarly inhibited NPY Y1 receptor augmentation of ATP-stimulated IP production (a measure of phospholipase C activity), a step thought to precede the NPY Y1 receptor-augmented protein kinase C-dependent AA release previously observed in these cells. These experiments demonstrate that G beta gamma subunits, as inhibited by two different G beta gamma scavengers, significantly contribute to the synergistic interaction between NPY Y1 Gi/o- and Gq/11-coupled receptor activity, and are required for the augmentation of IP production and AA release observed in this model cell system.
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PMID:Role of G-protein beta gamma subunits in the augmentation of P2Y2 (P2U)receptor-stimulated responses by neuropeptide Y Y1 Gi/o-coupled receptors. 935 46

The literature describing the expression of 5-HT receptor subtypes by astrocytes is controversial and incomplete. It is clear that primary cultures of astrocytes express receptors of the 5-HT2 family coupled to phospholipase C and of the 5-HT7 receptor family positively coupled to adenylyl cyclase. Cultured astrocytes have also been reported to express receptors of the 5-HT1 family, although the exact subtypes present are unknown. In the present study we have investigated which of the known rat G-protein coupled 5-HT receptor mRNAs are expressed by cultured astrocytes. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed expression of 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT5B, 5-HT6 and 5-HT7 receptor mRNAs in astrocytes derived from 2-day old rats and cultured for 10-12 days. Messenger RNAs for 5-HT4 and 5-HT5A receptors were not detected. The functional expression of 5-HT1 receptor subtypes was investigated by measuring the ability of 5-HT1 receptor agonists: 8-OH-DPAT (5-HT1A receptors), RU24969 (5-HT1A, 5-HT1B, 5-HT1D, and 5-HT1F receptors) or sumatriptan (5-HT1B, 5-HT1D, and 5-HT1F receptors) to modulate forskolin or isoproterenol stimulated cAMP production. These compounds, at concentrations up to 10 microM, did not significantly attenuate cAMP production. These results indicate that although astrocytes express mRNA for each of the five 5-HT1 receptor subtypes which have been isolated from the rat, these receptors are not coupled to the inhibition of adenylyl cyclase.
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PMID:Cultured astrocytes express messenger RNA for multiple serotonin receptor subtypes, without functional coupling of 5-HT1 receptor subtypes to adenylyl cyclase. 979 56

Large arteries from hypertensive subjects are hyperresponsiveness to 5-hydroxytryptamine (5-HT). We tested the hypothesis that small arteries (225 micro ID) have a profile similar to conduit arteries, including signal transduction mechanisms and the 5-HT receptor subtype(s) mediating arterial contraction in normal and high blood pressure. Aorta and mesenteric arteries from Sprague-Dawley (232+/-6 micro ID), sham (229+/-7 micro ID; systolic blood pressure, 120+/-2 mm Hg), or deoxycorticosterone acetate (DOCA)-salt rats (255+/-11 micro ID, 192+/-8 mm Hg) were mounted in a wire-based myograph. In resistance arteries from Sprague-Dawley rats, the 5-HT2A receptor mediated contraction; agonists of the 5-HT1B, 5-HT1D, 5-HT1F, and 5-HT2B receptor were inactive. The tyrosine kinase inhibitor genistein (5 micromol/L, 4.8-fold rightward shift), PD 098,059 (10 micromol/L, 3.2-fold shift), phospholipase C inhibitor NCDC (100 micromol/L), and nifedipine (50 nmol/L) reduced maximum 5-HT-induced contraction in small arteries (4.5% and 53% control, respectively). As in aorta, 5-HT had a decrease in threshold (100-fold lower), increase in potency (11.6-fold leftward shift), and increase in efficacy (140% sham response) in small arteries from DOCA-salt rats compared with sham. Unlike in aorta, 5-HT-induced contraction in DOCA-salt small arteries was shifted competitively by the 5-HT2A receptor antagonist ketanserin (-log K(B) [mol/L] for both sham and DOCA-salt, 9.25+/-0.1), and contraction to the 5-HT2B agonist BW723C86 was not observed. Thus, the 5-HT2A receptor remains the contractile receptor in hypertension in small arteries. Although similarities were observed for large and small arteries, differences under the condition of DOCA-salt hypertension exist that may determine serotonergic compounds effective in lowering blood pressure.
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PMID:Serotonin-induced contraction in mesenteric resistance arteries: signaling and changes in deoxycorticosterone acetate-salt hypertension. 1189 72


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