Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.4.3 (phospholipase C)
18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelin-1 (ET-1) is synthesized and released by parathyroid epithelium. The effects of endothelin isopeptides were studied in clonal bovine parathyroid endothelial (BPE) cells. BPE cells did not produce ET-1, but showed ETA receptors (Kd = 0.1 +/- 0.02 nM, mean +/- SE). ET-1 (10(-8)10(-11)M) increased the intracellular calcium ion concentration ([Ca2+]i) in BPE cells, while endothelin-3 (ET-3) was ineffective. The increase in [Ca2+]i was less sustained in the absence of extracellular Ca2+ ions. Moreover ET-1 induced phospholipase C (PLC) activation, as demonstrated by the increase in inositol trisphosphate. Cell growth was not affected by ET-1 in a wide range of concentrations. The present findings demonstrate: 1) BPE cells possess ETA receptors; 2) the peptide activates PLC and increases cytosolic [Ca2+]i via both a release of Ca2+ ions from intracellular calcium pool(s) and an influx of the cation from the extracellular milieu. A possible role of ET-1 as a paracrine factor in parathyroid tissue can be hypothesized.
...
PMID:Effects of endothelin-1 on bovine parathyroid cells. 850 38

The regulation of the inositide signalling pathway and [Ca2+]i by endothelin (ET) peptides was investigated in human glomerular epithelial cells in culture. Endothelin-1 and -2 induced an accumulation of inositol phosphates in a time- and dose-dependent manner. The baseline of [Ca2+]i in glomerular epithelial cells was 109 +/- 2.8 nmol/l, n = 60. Endothelin-1 (ED50: approx. 3 x 10(-9) mol/l) caused a rapid and transient rise in [Ca2+]i as detected by fura-2 microfluorimetry studies. The endothelin-1-induced inositol phosphate accumulation was inhibited by the selective ETA receptor antagonist BQ123. Endothelin-3 and BQ3020, a selective ETB receptor agonist, showed no effect. The results suggest an ETA-mediated pathway. This study demonstrates an ETA-mediated transmembrane signalling via phospholipase C with consecutive elevation of inositol phosphates and intracellular calcium. Since endothelin peptides contribute to both normal renal function and renal dysfunction, this study adds further knowledge on glomerular cell regulation.
...
PMID:Regulation of phosphoinositide hydrolysis and cytosolic free calcium induced by endothelin in human glomerular epithelial cells. 853 18

In the current study, endothelin-1 (ET-1) worked as a mitogen on Chinese hamster ovary cells stably expressing human endothelinA; when applied to serum-deprived cells, ET-1 caused dose-dependent increase in [3H]thymidine incorporation and cell proliferation. No synergism was observed between the effect of ET-1 and that of insulin-like growth factor-1/basic fibroblast growth factor. Both the inhibition of intracellular Ca2+ response by phospholipase C inhibitor U73122 and the down-regulation of protein kinase C (PKC) by pretreatment with phorbol 12-myristate-13-acetate (PMA) partially blocked the ET-1-induced mitogenic responses. Wortmannin, a phosphatidylinositol-3-kinase inhibitor, caused dose-dependent inhibition of the ET-1-induced mitogenic responses in both PMA-treated and -untreated cells. Wortmannin also inhibited ET-1-induced increase in phosphatidylinositol trisphosphate formation and activation of mitogen-activated protein kinase (MAPK), whereas it failed to inhibit PMA-induced activation of MAPK. In accordance with its effect on MAPK activation, wortmannin inhibited ET-1-induced activation of Raf-B, whereas it failed to inhibit the effect of PMA. These results suggested the role of a Ca2+/PKC-independent, wortmannin-sensitive signaling pathway that linked ETA and MAPK cascade in the mitogenic signaling activated by ETA.
...
PMID:Endothelin-1-induced mitogenic responses of Chinese hamster ovary cells expressing human endothelinA: the role of a wortmannin-sensitive signaling pathway. 864 84

Phospholipid signalling mediated by endothelin (ET) receptor subtypes was studied in the rat proximal tubule. In freshly isolated proximal tubule cells, ET-1, ET-2 and sarafotoxin S6c (S6c) evoked an increase in 1,2-diacylglycerol (DAG), inositol 1,4,5-trisphosphate (InsP3) and phosphocholine (PCho), suggesting stimulation of both phosphatidyl-inositol 4,5-bisphosphate- and phosphatidyl-choline-specific phospholipase C (PLC), while ET-3 increased only DAG and PCho, presumably via phosphatidyl-choline-dependent PLC. Renal cortical slices were also stimulated by the above-mentioned agonists, followed by isolation of either brush border (BBM) or basolateral (BLM) membranes for which mass measurements of inositol lipids and DAG were performed. In BBM, DAG increased in response to ET-1, ET-2 and ET-3, and was followed by protein kinase C (PKC) translocation to the BBM, while in BLM, DAG formation and translocation of PKC were observed only in response to ET-3, suggesting spatial segregation of signalling systems between two membane domains of proximal tubule cells. Tyrphostine, pertussis toxin (PTX) or cholera toxin (CTX) did not influence ET-mediated signalling in either of the membranes, suggesting involvement of PTX- and CTX-insensitive G-protein-mediated stimulation of PLCbeta by ET receptors. ET-dependent stimulation of PLC in BBM and BLM was used as a tool to examine the presence of different ET receptor subtypes in these two cell membrane domains. BQ123, an inhibitor of ETA receptors, did not prevent ET-1-mediated signalling in BBM, but an ETA,B antagonist, bosentan, inhibited ET-3-mediated signalling in BBM. In addition, an ETB agonist, S6c, stimulated PLC in BBM. Neither BQ123 nor bosentan inhibited ET-3 signalling in BLM. Therefore, these data strongly suggest the presence of ETB receptors coupled to phosphatidyl-inositol 4,5-bisphosphate- and phosphatidyl-choline-dependent PLC in BBM and ETC receptors linked to phosphatidyl-choline-dependent PLC in BLM.
...
PMID:Different endothelin receptor subtypes are involved in phospholipid signalling in the proximal tubule of rat kidney. 866 90

Et-1 and Et-3 activate phospholipase C in fibroblasts expressing cloned ETA receptors of bovine, rat and human origins. BQ-123 competitively antagonizes both responses but Et-3 actions are 10 times more sensitive to BQ-123 than Et-1 actions. It is suggested that differential sensitivity to BQ-123 is an intrinsic property of Et-1 and Et-3 activated ETA receptors and that there is no need to postulate the existence of new ETA receptor isoforms to account for singular actions of BQ-123.
...
PMID:Et-1 and Et-3 actions mediated by cloned ETA endothelin receptors exhibit different sensitivities to BQ-123. 869 6

Endothelins (ETs) were initially thought to be primarily involved in the control of cardiovascular activity, but the presence of ETs and their receptors in a wide variety of other tissues has suggested a much broader range of functions. Specific receptors for ETs are found in nonvascular tissues including neuronal, neuroendocrine, and endocrine cells. In addition, immunoreactive ETs are present in the brain, pituitary, and peripheral endocrine tissues. However, the ET levels in hypothalamo-hypophysial portal and peripheral blood are low, suggesting that the ET system participates in neuroendocrine regulation through paracrine and/or autocrine mechanisms. Both ETA and ETB receptors are expressed in the hypothalamus, adrenal, parathyroid glands, pancreas, ovary, uterus, placenta, and prostate, while only ETA receptors are expressed in GT1 neurons, anterior pituitary cells, alpha T3-1 immortalized gonadotropes, parathyroid-derived cells, thyrocytes, testicular Leydig and Sertoli cells, normal and neoplastic ovarian granulosa cells, chondrocytes, and other cell types. Activation of ET receptors elicits the sequence of cellular events typical of Ca(2+)-mobilizing receptors, with prominent increases in phosphoinositide hydrolysis and elevations of [Ca2+]i that occur in oscillatory and nonoscillatory modes depending on the cell type. ET-induced activation of the phosphoinositide/Ca(2+)- mobilizing pathway in neuronal and endocrine cells is associated with rapid stimulation of secretory responses, including release of gonadotropin-releasing hormone, oxytocin, vasopressin, substance P, atrial natriuretic peptides, gonadotropins, thyrotropin, growth hormone, parathyroid hormone, aldosterone, and catecholamines. On the other hand, ET has inhibitory actions on prolactin, progesterone, and renin release. In addition to stimulating phospholipase C-dependent pathways, ETs also activate phospholipase D-and MAP-kinase-dependent pathways in some of their target cells, as well as expression of early response genes and increased mitogenic activity. In many neuroendocrine cells, ET induces rapid and marked desensitization of its signaling system, in association with extensive internalization of ET receptors and reduced signaling and secretory responses. These findings raise the possibility that ETs participate in the control of secretory responses in the hypothalamo-pituitary system and peripheral endocrine cells, as well as in long-term aspects of regulation in certain neuroendocrine cells.
...
PMID:Expression and signal transduction pathways of endothelin receptors in neuroendocrine cells. 881 99

We investigated the vascular effects and mechanism of action of endothelin-1 (ET-1) in the skin by intra-arterial infusion of ET-1 and its precursor Big ET-1 via a direct cutaneous artery in isolated perfused pig skin flaps (6 x 16 cm). The vascular contractivity was studied by monitoring the perfusion pressure in the skin flap. There was evidence to indicate local conversion of Big ET-1 to ET-1 in the pig skin. It was also observed that ET-1 was a potent long-lasting vasoconstrictor with a potency of approximately 10- and 300-fold higher than those of Big ET-1 and norepinephrine, respectively. The vasoconstrictor action of ET-1 was blocked (P < 0.01) by a selective ETA-receptor antagonist (BQ-123 or BQ-610; 10(-7) M) and enhanced (P < 0.05) by a nitric oxide synthase inhibitor (NG-monomethyl-L-arginine or N omega-nitro-L-arginine methyl ester; 10(-5) M). ET-1-induced increase in perfusion pressure was attenuated (P < 0.05) by an L-type Ca(2+)-channel antagonist (nitrendipine, verapamil, or nifedipine; 10(-5) M) and by removal of Ca2+ from the perfusate. ET-1-induced increase in perfusion pressure was also attenuated (P < 0.05) by a phospholipase C inhibitor (neomycin; 10(-2) M), a protein kinase C (PKC) inhibitor (chelerythrine or H-7; 10(-5) M), and an intracellular Ca2+ chelator [1,2-bis(2-aminophenoxy)]ethane-N,N,N',N'-tetraacetic acid (BAPTA); 10(-5) M]. Furthermore, it was observed that the concentration-dependent (5 x 10(-8) to 10(-5) M) increase in perfusion pressure induced by phorbol 12,13-dibutyrate, a PKC activator, was not affected by verapamil (10(-5) M) or removal of Ca2+ from the perfusate. Taken together, these observations suggest that the vasoconstrictor mechanism of ET-1 in the pig skin involved activation of ETA receptors, L-type Ca2+ channels, phospholipase C, and PKC and that the vasoconstrictor effect caused by activation of PKC was independent of L-type Ca2+ channels.
...
PMID:Vascular effects and mechanism of action of endothelin-1 in isolated perfused pig skin. 884 80

In both immortalized cat iris sphincter smooth muscle cells (SV-CISM-2 cells) and cat iris sphincter, endothelin-1 (ET-1) markedly increased the activities of phospholipase A2 (PLA2), as measured by the release of arachidonic acid (AA), phospholipase C (PLC), as measured by the production of inositol trisphosphate (IP3), and phospholipase D (PLD), as measured by the formation of phosphatidylethanol (PEt). In SV-CISM-2 cells, ET-1 induced AA release, IP3 production and PEt formation in a dose- and time-dependent manner. The dose-response studies showed that the peptide is more potent in activating PLD (EC50 = 1.2 nM) than in activating PLC (EC50 = 1.5 nM) or PLA2 (EC50 = 1.7 nM). The time course studies revealed that ET-1 activated the phospholipases in a temporal sequence in which PLA2 was stimulated first (t1/2 = 12 s), followed by PLC (t1/2 = 48 s) and lastly PLD (t1/2 = 106 s). In SV-CISM-2 cells, in contrast to the intact iris sphincter, sarafotoxin-c, an ETB receptor agonist, had no effect on the phospholipases, and indomethacin, a cyclooxygenase inhibitor, had no effect on the stimulatory effect of ET-1 on the phospholipases. These results suggest that in this smooth muscle cell line, ET-1 interacts with the ETA receptor subtype to activate, via G proteins, phospholipases A2, C and D in a temporal sequence.
...
PMID:Effects of endothelin on phospholipases and generation of second messengers in cat iris sphincter and SV-CISM-2 cells. 890 57

Testicular myoid cells surrounding the seminiferous tubule are contractile cells responsible for peritubular contractility and for the propulsion of tubular fluid and spermatozoa. We have investigated the contractile response of rat myoid cells to endothelins (ETs) in cell and organ culture and analyzed the cell signaling involved. ET-2, ET-3, and IRL 1620, a highly selective agonist of ETB receptor, elicit [Ca2+]i increases, though with dissimilar potencies and kinetics. Competition binding assays using [125I]ET-1, [125I]ET-3 and [125I]IRL 1620 show that myoid cells express both ETA and ETB receptors with high affinity for ET-1 and ET-1/ ET-3, respectively. All endothelin isoforms activate phosphoinositide (PI) turnover, but only stimulation of the ETA receptor mediates both PI turnover and mobilization of [Ca2+]i. Although stimulation of the ETB receptor with IRL 1620 fails to produce a significant effect on inositol phosphate (IP) production, it induces mobilization of a thapsigargin-sensitive intracellular Ca2+ pool in the absence of any measurable IP production. We also studied the effect of U-73122 [1-(6-[17-beta-3-methoxyestra-1,3,5 (10)-trien-17-yl] amino/hexyl)-1H-pirrole-2,5-dione] and its inactive analog, U-73343, on Ca2+ mobilization and IP production after selective stimulation of ET receptors. U-73122 (1 microM) completely inhibited the effect of ETA-mediated ET-1 stimulation of IP production, whereas U-73343 was inactive. However, in the presence of U-73122, the selective stimulation of ETB receptors induced the mobilization of a thapsigargin-sensitive and inositol phosphate-independent intracellular Ca2+ pool. The ETB receptor-dependent mobilization of [Ca2+]i resulted mainly from Ca2+ release from intracellular Ca2+ stores. This paper illustrates contraction of myoid cells in the seminiferous tubule in response to selective activation of either ET receptor. Scanning electron microscopy of the peritubular tissue demonstrates that the contractile response to ET was inhibited by a combination of BQ-123 and BQ-788, but not by either antagonist alone. Moreover, the observation that selective stimulation of ETB receptor with IRL 1620 also resulted in cell contraction strongly suggests that stimulation of either ETA or ETB receptors alone may be sufficient to elicit seminiferous tubule contractility. Two types of receptors account for the actions of endothelin on contractile activity of seminiferous tubule: 1) an ETA receptor that is positively coupled to phospholipase C (PLC) and Ca2+ mobilization; and 2) an ETB receptor that induces the mobilization of a thapsigargin-sensitive intracellular Ca2+ pool in a manner independent of the formation of inositol phosphates. ET may play a complex role in regulating the flux of spermatozoa along the seminiferous tubule through its contractile effect on peritubular myoid cells.
...
PMID:Dual control of seminiferous tubule contractility mediated by ETA and ETB endothelin receptor subtypes. 906 17

1. Endothelin-1 (ET-1) production from endothelial cells is generally believed to be a process that happens over the course of hours. 2. When fluoroaluminate (AIF-4) was infused in the isolated perfused arterial and venous vessels of the rat mesentery there was an increase in perfusion pressure on both sides. 3. Treatment of mesentery with the endothelin receptor antagonists FR 139317 (ETA receptor selective) or PD 145065 (ETA-ETB receptor nonselective) caused inhibition on both the arterial and venous sides, suggesting that response is mediated predominantly by endothelin-1 through ETA receptors. 4. Endothelial denudation attenuated changes in perfusion pressure of mesenteric circulation generated by fluoroaluminate, but not those caused by exogenously added PGF2 alpha. 5. Our data demonstrate that there is an immediate release of endothelin-1 following fluoroaluminate infusion which could be partially mediated by activation of phospholipase C.
...
PMID:Fluoroaluminate induces rapid release of endothelin-1 in the isolated perfused arterial and venous vessels of the rat mesentery. 906 91


<< Previous 1 2 3 4 5 6 7 Next >>

---