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)

Effects of endothelin-3 on ganglionic transmission were investigated in dog cardiac sympathetic ganglia. Positive chronotropic responses to preganglionic stellate stimulation were inhibited by endothelin-3 (0.5-2 micrograms) given directly to the ganglia through the artery. To find possible inhibitory effects of the peptide at presynaptic sites, acetylcholine released from the isolated stellate ganglia was determined. The amount of acetylcholine released during preganglionic stimulation was reduced by exposure to endothelin-3 (10(-9) to 10(-6) M). A similar reduction of acetylcholine release was observed after application of a stable thromboxane A2, a thromboxane A2/prostaglandin H2 receptor agonist, U-46619, and prostaglandin E2 at concentrations from 10(-8) to 10(-4) M, but not by the same concentrations of prostaglandins F2 alpha and I2. The reduction elicited by endothelin-3 was unaffected by a phospholipase C inhibitor, neomycin, or a protein kinase C inhibitor, H-7, but was antagonized by pretreatment with phospholipase A2 inhibitors, dexamethasone or methylprednisolone, and by cyclooxygenase inhibitors, aspirin and indomethacin. In addition, the reduction also was antagonized by pretreatment with a thromboxane A2 synthetase inhibitor, OKY-046, and a specific thromboxane A2 receptor antagonist, S-145, but not by a specific prostaglandin E2 receptor antagonist, SC-19220. Furthermore, endothelin-3 (10(-7) M) stimulated the OKY-046- and indomethacin-sensitive formation of thromboxane A2 in the ganglia. These results indicate that endothelin-3 inhibits the sympathetic ganglionic transmission by reducing acetylcholine release at preganglionic terminals and that this inhibition seems to involve activation of endogenous thromboxane A2 production.
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PMID:Activation of endogenous thromboxane A2 biosynthesis mediates presynaptic inhibition by endothelin-3 of dog stellate ganglionic transmission. 781 66

The functional activity of G protein-coupled receptors can be modified by their ability to form oligomeric complexes with G protein-coupled receptors from other receptor families. Emerging evidence suggests that the appetite-regulating hormone ghrelin is a directly acting vasodilator peptide with anti-inflammatory activity, therefore, we have examined the ability of ghrelin receptors to oligomerize with members of the prostanoid receptor family which are also involved in modulating vascular activity and inflammatory responses. Using the techniques of bioluminescence resonance energy transfer and co-immunoprecipitation, we detected the ability of ghrelin receptors to hetero-oligomerize with prostaglandin E2 receptor subtype EP3-I, prostacyclin receptors, and thromboxane A2 (TPalpha) receptors, when transiently over-expressed in human embryonic kidney 293 cells. These results suggest that hetero-oligomeric interactions between ghrelin receptors and prostanoid receptors are likely to be of biological relevance. Co-transfection of cells with ghrelin receptor and prostanoid receptors significantly decreased ghrelin receptor expression and attenuated its constitutive activation of phospholipase C without changing its affinity for ghrelin. We also observed an increase in the proportion of ghrelin receptors localized intracellularly in the presence of prostanoid receptors. Taken together, these results suggest that the increased expression of prostanoid receptors in conditions of vascular inflammation, such as in atherosclerotic plaques, could influence those cellular responses dependent on the constitutive activation of ghrelin receptors.
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PMID:The constitutive activity of ghrelin receptors is decreased by co-expression with vasoactive prostanoid receptors when over-expressed in human embryonic kidney 293 cells. 1857 79

Prostaglandin E2 (PGE2) regulates membrane excitability, synaptic transmission, plasticity, and neuronal survival. The consequences of PGE2 release following seizures has been the subject of much study. Here we demonstrate that the prostaglandin E2 receptor 1 (EP1, or Ptger1) modulates native kainate receptors, a family of ionotropic glutamate receptors widely expressed throughout the central nervous system. Global ablation of the EP1 gene in mice (EP1-KO) had no effect on seizure threshold after kainate injection but reduced the likelihood to enter status epilepticus. EP1-KO mice that did experience typical status epilepticus had reduced hippocampal neurodegeneration and a blunted inflammatory response. Further studies with native prostanoid and kainate receptors in cultured cortical neurons, as well as with recombinant prostanoid and kainate receptors expressed in Xenopus oocytes, demonstrated that EP1 receptor activation potentiates heteromeric but not homomeric kainate receptors via a second messenger cascade involving phospholipase C, calcium and protein kinase C. Three critical GluK5 C-terminal serines underlie the potentiation of the GluK2/GluK5 receptor by EP1 activation. Taken together, these results indicate that EP1 receptor activation during seizures, through a protein kinase C pathway, increases the probability of kainic acid induced status epilepticus, and independently promotes hippocampal neurodegeneration and a broad inflammatory response.
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PMID:The prostaglandin EP1 receptor potentiates kainate receptor activation via a protein kinase C pathway and exacerbates status epilepticus. 2495 62

EP3 is prostaglandin E2 receptor subtype 3 and mediates the activation of several signaling pathways, changing in cAMP levels, calcium mobilization, and activation of phospholipase C. Previous studies demonstrated a direct role for EP3 in various neurodegenerative disorders, such as stroke and Alzheimer disease. However, the distribution and function of EP3 in ICH diseases remain unknown. Here, we demonstrate that EP3 may be involved in neuronal apoptosis in the processes of intracerebral hemorrhage (ICH). From the results of Western blot and immunohistochemistry, we obtained a significant up-regulation of EP3 in neurons adjacent to the hematoma following ICH. Up-regulation of EP3 was found to be accompanied by the increased expression of active caspase-3 and pro-apoptotic Bcl-2-associated X protein (Bax) and decreased expression of anti-apoptotic protein B cell lymphoma-2 (Bcl-2) in vivo and vitro studies. Furthermore, the expression of these three proteins reduced active caspase-3 and Bax expression, while increased Bcl-2 were changed after knocking down EP3 by RNA interference in PC12 cells, further confirmed that EP3 might exert its pro-apoptotic function on neuronal apoptosis. Thus, EP3 may play a role in promoting the neuronal apoptosis following ICH.
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PMID:EP3, Prostaglandin E2 Receptor Subtype 3, Associated with Neuronal Apoptosis Following Intracerebral Hemorrhage. 2671 10