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

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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)

We examined the regulation by adenosine of a 305-pS chloride (Cl-) channel in the apical membrane of a continuous cell line derived from rabbit cortical collecting duct (RCCT-28A) using the patch clamp technique. Stimulation of A1 adenosine receptors by N6-cyclohexyladenosine (CHA) activated the channel in cell-attached patches. Phorbol 12,13-didecanoate and 1-oleoyl 2-acetylglycerol, activators of protein kinase C (PKC), mimicked the effect of CHA, whereas the PKC inhibitor H7 blocked the action of CHA. Stimulation of A1 adenosine receptors also increased the production of diacylglycerol, an activator of PKC. Exogenous PKC added to the cytoplasmic face of inside-out patches also stimulated the Cl- channel. Alkaline phosphatase reversed PKC activation. These results show that stimulation of A1 adenosine receptors activates a 305-pS Cl-channel in the apical membrane by a phosphorylation-dependent pathway involving PKC. In previous studies, we showed that the protein G alpha i-3 activated the 305-pS Cl- channel (Schwiebert et al. 1990. J. Biol. Chem. 265:7725-7728). We, therefore, tested the hypothesis that PKC activates the channel by a G protein-dependent pathway. In inside-out patches, pertussis toxin blocked PKC activation of the channel. In contrast, H7 did not prevent G protein activation of the channel. We conclude that adenosine activates a 305-pS Cl- channel in the apical membrane of RCCT-28A cells by a membrane-delimited pathway involving an A1 adenosine receptor, phospholipase C, diacylglycerol, PKC, and a G protein. Because we have shown, in previous studies, that this Cl- channel participates in the regulatory volume decrease subsequent to cell swelling, adenosine release during ischemic cell swelling may activate the Cl-channel and restore cell volume.
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PMID:Adenosine regulates a chloride channel via protein kinase C and a G protein in a rabbit cortical collecting duct cell line. 131 18

The inner medullary collecting duct is a complex tissue that exhibits a variety of hormone signaling systems. These include the following: adenylyl cyclase activity stimulated by vasopressin (AVP), beta-adrenergic agonists, or prostanoids and inhibited by alpha 2-adrenergic agents or adenosine; guanylate cyclase activity in response to atrial natriuretic peptide (ANP); phospholipase C activity stimulated by ANP, AVP, bradykinin, endothelin, epidermal growth factor (EGF), and muscarinic cholinergic agents; and phospholipase A2 activity stimulated by AVP, bradykinin, EGF, and endothelin. The signal transduction mechanisms for each of these hormone signaling systems is succinctly reviewed, and the interactions between different signaling pathways are discussed. Central to this interaction is the mutually inhibitory relationship between activation of adenylyl cyclase and phospholipases. Increasing cellular adenosine 3',5'-cyclic monophosphate content impairs activation of phospholipases A2 and C; conversely, stimulation of phospholipase C impairs AVP-stimulated adenylyl cyclase activity via activation of protein kinase C.
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PMID:Hormone signaling systems in inner medullary collecting ducts. 136 28

Growth hormone (GH) and insulin-like growth factor I (IGF-I) exert a variety of actions in renal tissue. To shed light upon the renal GH-IGF I axis we have characterized the cell biology of GH and IGF I in two parts of the nephron that are targets for these peptides, proximal tubule and collecting duct. Receptors for both GH and IGF I are present in the basolateral membrane of the renal proximal tubular cell. GH activates phospholipase C and IGF I stimulates phosphorylation of its receptor at this site. Both peptides directly enhance gluconeogenesis in proximal tubule. GH stimulates IGF I gene expression in collecting duct. IGF I of collecting duct origin could act as a paracrine growth factor in other portions of the nephron. IGF I may be causative of renal hypertrophy that occurs in the settings of hypersomatotropism, unilateral nephrectomy (compensatory hypertrophy) and diabetes mellitus.
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PMID:Renal cellular biology of growth hormone and insulin-like growth factor I. 165 79

The renal collecting duct is a site of insulin-like growth factor I (IGF I) synthesis. Epidermal growth factor (EGF) is also synthesized within the kidney in the thick ascending limb of Henle's loop and the distal tubule. EGF has been shown to regulate IGF I expression in nonrenal tissues. To shed light upon a role of EGF in intrarenal regulation of IGF I gene expression, plasma membranes prepared from collecting ducts isolated from rat kidney and collecting ducts themselves were incubated in the presence and absence of recombinant human EGF (hEGF). hEGF enhanced phospholipase C activity in collecting duct plasma membranes establishing the potential for EGF signal transduction at this site. Inclusion of hEGF in suspensions of collecting ducts increased production of immunoreactive IGF I in a concentration-dependent manner. Production was stimulated significantly by addition of 10(-8) or 10(-6) M hEGF to suspensions for 2 h. Levels of IGF I mRNA in collecting ducts were increased 2.8-fold after incubation with 10(-6) M hEGF in vitro. Our findings demonstrate a direct action of hEGF to enhance collecting duct IGF I gene expression in vitro. Such enhancement is likely to reflect an effect of EGF to stimulate IGF I production in the collecting duct of the intact kidney. Since EGF is produced in kidney, our findings are consistent with intrarenal paracrine regulation of IGF I gene expression by EGF.
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PMID:Insulin-like growth factor I gene expression in isolated rat renal collecting duct is stimulated by epidermal growth factor. 198 6

Epidermal growth factor (EGF) exhibits specific saturable binding to cultured rat inner medullary collecting tubule cells and stimulates inositol trisphosphate (IP3) production by these cells in a dose-dependent fashion. EGF-stimulated IP3 production is enhanced by GTP gamma s or AIF4- and is inhibited by GDP beta s or pertussis toxin. Alterations in extracellular Ca2+ have no effect on either basal or EGF-stimulated IP3 production. Similarly, treatment with EGTA which decreases cytosolic Ca2+ is without effect. In contrast, treatment with ionomycin which increases cytosolic Ca2+ has no effect on basal IP3 production but enhances the response to EGF. Activation of protein kinase C inhibits IP3 production in response to either EGF or AIF4-. These studies demonstrate the occurrence of EGF-stimulated phospholipase C activity in the rat inner medullary collecting duct. Stimulation by EGF is transduced by a pertussis toxin-sensitive G protein, unaffected by alterations in extracellular Ca2+, insensitive to a decrement in cytosolic Ca2+, enhanced by an increase in cytosolic Ca2+, and inhibited by protein kinase C.
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PMID:Epidermal growth factor-stimulated phosphoinositide hydrolysis in cultured rat inner medullary collecting tubule cells. Regulation by G protein, calcium, and protein kinase C. 215 92

Studies were performed to examine interactions between the adenylyl cyclase (AC) and phospholipase C (PLC) signaling systems in cultured rat inner medullary collecting duct cells. Stimulation of AC by either arginine vasopressin (AVP) or forskolin or addition of exogenous cAMP inhibits epidermal growth factor (EGF)-stimulated PLC. This inhibition is mediated by activation of cAMP-dependent kinase as it is prevented by pretreatment with the A-kinase inhibitor, N-[2-(methylamino)ethyl]-5-isoquinoline-sulfonamide (H8) but not by the C-kinase inhibitor, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7). Exposure to EGF eliminates AVP-stimulated cAMP generation. This is not mediated by a cyclooxygenase product as inhibition by EGF is observed even in the presence of the cyclooxygenase inhibitor, flurbiprofen. Inhibition by EGF is not due to an increase in inositol trisphosphate (IP3) as exposure of saponin-permeabilized cells to exogenous IP3 is without effect. Inhibition by EGF is prevented by pretreatment with the C-kinase inhibitor, H7, but not by the A-kinase inhibitor, H8. Exposure to the synthetic diacylglycerol (DAG), dioctanoylglycerol, also inhibits AVP-stimulated AC activity; therefore, inhibition by EGF is due to activation of protein kinase C. Thus, in cultured rat inner medullary collecting duct cells, cAMP and DAG function as mutually inhibitory second messengers with each impairing formation of the other.
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PMID:Cyclic adenosine monophosphate and diacylglycerol. Mutually inhibitory second messengers in cultured rat inner medullary collecting duct cells. 216 48

Arginine vasopressin (AVP) interacts with V1 and V2 receptors to stimulate hydrolysis of phosphoinositides (PI) and formation of cAMP, respectively. The effects of AVP on V2 receptors in the kidney are well characterized. In order to determine whether V1 receptors, coupled to phospholipase C for hydrolysis of PI, are also present in the kidney, we investigated the effects of AVP on PI hydrolysis in tissue slices from the cortex, outer medulla, and inner medulla of the rabbit kidney. We found that 10(-6) M AVP produced a significant increase in PI hydrolysis in the inner and outer medulla but not in the cortex. In the inner medulla, AVP (10(-10) M) produced a greater than 50% increase in PI hydrolysis; the effect was much greater at higher concentrations. AVP-stimulated PI hydrolysis was blocked by a V1 antagonist but not by a V2 antagonist. Increasing the osmolality of the incubation to 600 mosmol/kg water also abolished the effect of AVP on PI hydrolysis in the inner medulla. Furthermore, AVP did not stimulate PI hydrolysis (even in isoosmotic media) in isolated inner medullary collecting duct cells which make a major portion of the inner medulla. Our results indicate: 1) V1 receptors linked to PI system are not present in the inner medullary collecting duct cells but are probably present in blood vessels and/or interstitial cells of the renal medulla; and 2) AVP-stimulated PI hydrolysis in the inner medulla is modulated by the osmolality of the extracellular fluid.
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PMID:Stimulation of phosphoinositide hydrolysis in renal medulla by vasopressin. 216 2

In this study we investigated the role of protein kinases in activation of the Na(+)-H+ exchanger in inner medullary collecting duct (IMCD) cells. Monolayers, 24-48 h after achieving confluence, were made quiescent by 24 h incubation in 0.1% serum before study. Changes in pHi were measured with 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. Phorbol myristate acetate (PMA), a synthetic analogue of diacylglycerol (DAG), was used to stimulate protein kinase C (PKC). In nominally HCO3(-)-free media containing 110 mM Na+ and 1 mM Ca2+, PMA addition increased pHi from 7.29 +/- 0.08 to 7.54 +/- 0.07 after 20 min. The increment in pHi was completely inhibited by 1 mM amiloride or by replacement of extracellular Na+ with choline but not inhibited by 1 mM N-ethylmaleimide, an inhibitor of active proton transport. Downregulation of PKC by overnight incubation of monolayers with PMA also prevented the rise in pHi upon subsequent challenge with PMA. Another active analogue of DAG, 1,2-dioleoyl-rac-glycerol, caused an increment in pHi similar to that produced by PMA, whereas 4 alpha-phorbol, an inactive analogue, did not stimulate Na(+)-H+ exchange. Bradykinin (10(-6) M), a phospholipase C-activating hormone, also induces alkalinization of IMCD cells similar to that produced by phorbol esters. Neither vasopressin (10(-7) M), which induces cellular accumulation of adenosine 3',5'-cyclic monophosphate (cAMP) and activation of protein kinase A (PKA), nor 8-bromo-cAMP (1 mM) changed pHi. Therefore in the IMCD cell activation of PKC but not PKA stimulates a rise in pHi via the Na(+)-H+ exchanger.
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PMID:Na(+)-H+ exchange is stimulated by protein kinase C activation in inner medullary collecting duct cells. 217 60

To determine whether growth hormone (GH) directly stimulates insulin-like growth factor I (IGF I) gene expression in renal collecting duct, plasma membranes prepared from collecting ducts isolated from rat kidney, and collecting ducts themselves were incubated in presence and absence of GH. GH enhanced phospholipase C activity in collecting duct plasma membranes establishing the potential for GH-signal transduction. Inclusion of GH in suspensions of collecting ducts increased production of immunoreactive IGF I in a time-dependent and concentration-dependent manner. Production was stimulated significantly by addition of 10(-10), 10(-8), or 10(-6) M GH to suspensions for 2 h. IGF I produced in isolated collecting ducts was released into the suspending media. Levels of IGF I mRNA in collecting ducts were increased 2.8-fold after incubation with 10(-6) M GH in vitro. IGF I of collecting duct origin was indistinguishable from recombinant human IGF I in terms of its size and receptor-binding characteristics. Our findings demonstrate a direct action of GH to enhance collecting duct IGF I gene expression in vitro. Such enhancement is likely to reflect the mechanism by which GH stimulates renal IGF I production in intact kidney.
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PMID:Growth hormone stimulates IGF I gene expression in isolated rat renal collecting duct. 239 72

The association of hepatocyte growth factor (HGF) with its high-affinity receptor, c-met, has been shown to induce mitogenesis, motogenesis, and morphogenesis in renal epithelial cells (L. G. Cantley, E. J. G. Barros, M. Gandhi, M. Rauchman, and S. K. Nigam. Am. J. Physiol. 267 (Renal Fluid Electrolyte Physiol. 36): F271-F280, 1994), suggesting that HGF may be critical to the orchestration of both renal development and regeneration following injury. Although signal transduction pathways activated by c-met include the phosphatidylinositol 3-kinase (PI-3-kinase), phospholipase C gamma, ras, and others, the activation of PI-3-kinase has been the most striking in vivo. We therefore investigated whether the pathways that mediate phenotypic changes in inner medullary collecting duct cells are altered by inhibition of PI-3-kinase with the fungal metabolite, wortmannin. In these cells, the mean inhibitory concentration for in vitro wortmannin inhibition of PI-3-kinase was approximately 0.2 nM. At this low concentration, motogenesis (quantified by chemotaxis) and morphogenesis (by branching-process formation within collagen matrix) were inhibited in a striking and parallel fashion, while mitogenesis was inhibited to a lesser degree. These experiments suggest that activation of PI-3-kinase is critical for c-met-mediated chemotaxis and tubulogenesis.
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PMID:HGF-mediated chemotaxis and tubulogenesis require activation of the phosphatidylinositol 3-kinase. 761 61


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