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)

In the present study, we examined the relationship between endothelin receptors and phosphoinositide breakdown in muscle explants of placental stem villi vessels. All peptides examined, i.e. endothelin-1 (ET-1), ET-3, sarafotoxin 6b (S6b) and S6c, were able to induce phosphoinositide hydrolysis in a dose-dependent manner: ET-1 was more potent than S6b and ET-3, with corresponding EC50 values of 44 +/- 16 pmol/l, 18 +/- 13 nmol/l and 33 +/- 24 nmol/l, respectively. Sarafotoxin induced only moderate stimulation of inositol phosphate accumulation. Both ET-1- and S6b-induced accumulation of inositol phosphate was almost totally (90%) inhibited by 100 mumol/l BQ 123, while the S6c response was not affected by the ETA receptor antagonist. In contrast, the ETB receptor antagonist IRL 1038 inhibited S6c-induced inositol phosphate accumulation by more than 80%, whereas inhibition was only about 30% for ET-1 and S6b stimulations. This indicates that both ETA and ETB receptors were coupled to the phospholipase C transducing system in the muscular layer of placental stem villi vessels, and there is evidence that the phosphoinositide hydrolysis response is obtained predominantly via ETA receptor activation.
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PMID:Endothelin-induced phosphoinositide hydrolysis in the muscular layer of stem villi vessels of human term placenta. 758 92

Endothelin (ET) binding sites and phosphoinositide hydrolysis induced by ET peptides were studied in the nonpregnant human myometrium. Saturation binding experiments revealed that the proportion of [125I]ET-1 binding sites was 4-fold higher than that of [125I]ET-3 binding sites, whereas Kd values were not significantly different. In competition binding studies, unlabeled peptides displaced [125I]ET-1 binding with the following order of affinity ET-1 > sarafotoxin 6b > ET-3 >> sarafotoxin 6c, whereas very similar Ki values were obtained with the four peptides for the displacement of [125I]ET-3 binding. Approximately 75% of [125I]ET-1 binding sites exhibited high affinity to BQ 123 ([cyclo(D-Trp,D-Asp,L-Pro,D-Val,L-Leu)]), an ETA selective antagonist. ET-1 elicited a time-dependent accumulation of [3H]inositol phosphates in myometrial explants prelabeled with myo-[3H]inositol. All the peptides examined, ET-1, ET-3, sarafotoxin 6b and sarafotoxin 6c were able to induce phosphoinositide hydrolysis in a dose-dependent manner, ET-1 being more potent than ET-3 with corresponding EC50 values of 32 +/- 12 and 441 +/- 37 nM, respectively. Sarafotoxin 6c induced a moderate stimulation of inositol phosphates accumulation. ET-1- and ET-3-induced accumulation of [3H]inositol phosphates was (40-45%) inhibited in part by 100 microM BQ 123, whereas sarafotoxin 6c response was not affected by the ETA-antagonist. All these results indicate the presence of ETA and ETB receptors coupled to phospholipase C in human myometrium. Although ET-1 and ET-3 bind to both subtypes, sarafotoxin 6c only interacts with the ETB subtype.
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PMID:Endothelin receptors: binding and phosphoinositide breakdown in human myometrium. 793 9

We have investigated the possibility that ET-1 can induce an increase in myofilament calcium sensitivity in pulmonary artery smooth muscle. Arterial rings were permeabilized using alpha-toxin (120 microg ml(-1)), in the presence of A23187 (10 microM) to 'knock out' Ca2+ stores, and pre-constricted with pCa 6.8 (buffered with 10 mM EGTA). In the presence of this fixed Ca2+ concentration, 1 microM ET-1 induced a sustained, reversible constriction of 0.15 mN. Pulmonary arterial rings were freeze-clamped at the peak of the induced constriction (time matched). Subsequent densitometric analysis revealed that ET-1 (1 microM) increased the level of phosphorylated myosin light chains by 34% compared to an 11% increase in the presence of pCa 6.8 alone. In contrast to ET-1, the selective ET(B) receptor agonist Sarafotoxin S6C (100 nM) failed to induce a significant constriction. The constriction induced by 1 microM ET-1 was reversibly inhibited when the preparation was preincubated (15 min) with the ETA receptor antagonist BQ 123 (100 microM). The constriction measured 0.13 mN in the absence and 0.07 mN in the presence of 100 microM BQ 123. In contrast, the constriction induced by 1 microM ET-1 measured 0.19 mN in the absence and 0.175 mN following a 15 min pre-incubation with the ET(B) antagonist BQ 788 (100 microM). The constriction induced by 1 microM ET-1 measured 0.14 mN in the presence and 0.13 mN following pre-incubation with the tyrosine kinase inhibitor Tyrphostin A23 (100 microM). We conclude that ET-1 induced an increase in myofilament calcium sensitivity in rat pulmonary arteries via the activation of ET(A) receptors and by a mechanism(s) independent of tyrosine kinase.
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PMID:ET(A) receptors are the primary mediators of myofilament calcium sensitization induced by ET-1 in rat pulmonary artery smooth muscle: a tyrosine kinase independent pathway. 1036 68

We assessed the possible link between endothelin receptor mediated phosphoinositide breakdown and NO/cGMP signaling pathways in rat arcuate nucleus-median eminence fragments (AN-ME), brain structures known to contain a rich plexus of nitric oxide synthase (NOS)-containing neurons and fibers, together with densely arranged endothelin ETB-receptors-like immunoreactive fibres. Our data show that ET-1, ET-3 and the ETB-receptors agonist, IRL 1620, increased inositol monophosphate (InsP1) accumulation, NOS activity and cGMP formation, in a similar degree. The stimulatory effect of ETs on InsP1 accumulation and cGMP formation was inhibited by the phospholipase C (PLC) inhibitor, neomycin, and the absence of extracellular calcium, suggesting that calcium is involved in endothelin receptor-induced PLC activation. The L-arginine analog, L-NAME, inhibited ET-1 or IRL1620-stimulated cGMP formation. The ETA receptor antagonists BQ 123, did not alter, while the ETB receptor antagonists BQ788 inhibited ETs-induced increase in the PI metabolism, NOS activity and cGMP generation. Our data indicate that in AN-ME, ETB receptor signals through receptor-mediated calcium dependent-stimulation of phosphoinositide breakdown and activation of NOS/cGMP signaling pathway.
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PMID:Multiple signaling pathways involved in the effect of endothelin type B receptor in rat median eminence. 1758 4