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)

Human platelets stimulated by epinephrine undergo enhanced turnover of phosphatidylinositol 4,5-bisphosphate, accumulate inositol trisphosphate, diacylglycerol, and phosphatidic acid, and phosphorylate a 47-kDa protein. All of these phenomena indicate stimulation of phospholipase C. These responses are blocked completely by inhibitors of alpha 2-adrenergic receptors (yohimbine), cyclooxygenase (aspirin or indomethacin), phospholipase A [2-(p-amylcinnamoyl)amino-4-chlorobenzoic acid (ONO-RS-082)], Na+/H+ exchange [ethylisopropylamiloride (EIPA)], fibrinogen binding to glycoprotein IIb/IIIa (antibody A2A9), Ca2+/Mg+ binding (EDTA), or removal of fibrinogen. Epinephrine evokes (i) an increased turnover of ester-linked arachidonic acid in aspirin treated platelets that is inhibited by ONO-RS-082, EDTA, yohimbine, or the absence of fibrinogen and (ii) a rapid cytoplasmic alkalinization that is inhibited partially by blockage of cyclooxygenase activity and completely by A2A9 or EIPA. In contrast, when incubated with subaggregatory concentrations of the prostaglandin H2/thromboxane A2 analogue [(15S)-hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic acid (U46619) and epinephrine, aspirin-treated platelets show a potentiation of phospholipase C activation that is unaffected by the above inhibitors. We propose that epinephrine, in promoting exposure of glycoprotein IIb/IIIa sites for fibrinogen binding, leads to a cytoplasmic alkalinization, which, in conjunction with local shifts in Ca2+, promotes low-level activation of phospholipase A. The resulting free arachidonic acid is converted to cyclooxygenase products, which, potentiated by epinephrine, activate phospholipase C. This further amplifies the initial stimulatory response.
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PMID:Activation of phospholipases A and C in human platelets exposed to epinephrine: role of glycoproteins IIb/IIIa and dual role of epinephrine. 302 70

Isolated ductal cells of rat submandibular gland phospholipid pools were labeled with [3H]arachidonic acid (AA). The tracer was incorporated preferentially to phosphatidylcholine (46% of the lipidic fraction). Extracellular ATP induced the release of [3H]AA to the extracellular medium in a time- and dose-dependent manner (EC50 = 220 microM). Among other agents tested, only 2', 3'-O-(4-benzoylbenzoyl)adenosine 5'-triphosphate (Bz-ATP) was able to mimic the effect of ATP (EC50 = 15 microM), without activation of phospholipase C. The purinergic antagonists oxidized ATP, suramin, and Coomassie Blue partly inhibited the response to 1 mM ATP and 100 microM Bz-ATP; the response was also blocked by the addition of Mg2+ or Ni2+. Expression of P2X7 receptor mRNA in these cells was confirmed by reverse transcription-polymerase chain reaction. In the presence of extracellular calcium, the phospholipase A2 inhibitor 2-(p-amylcinnamoyl)amino-4-chlorobenzoic acid (a nonspecific inhibitor), arachidonyl trifluoromethylketone (AACOCF3, an inhibitor of the calcium-dependent cytosolic PLA2 (cPLA2)), and bromoenol lactone (an inhibitor of the calcium-independent PLA2 (iPLA2)) inhibited the release of [3H]AA induced by ATP and Bz-ATP. In the absence of extracellular calcium, the release of [3H]AA in response to the purinergic agonists was still observed; this response was not affected by AACOCF3 and completely blocked by bromoenol lactone. ATP and Bz-ATP stimulated a calcium-independent secretion of kallikrein, which could be blocked by BEL but which was enhanced by AACOCF3. It is concluded that the P2X7 receptor in ductal cells is coupled to kallikrein secretion through a calcium-dependent cPLA2 and a calcium-independent iPLA2.
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PMID:Activation by P2X7 agonists of two phospholipases A2 (PLA2) in ductal cells of rat submandibular gland. Coupling of the calcium-independent PLA2 with kallikrein secretion. 980 78

In order to examine some possibly misleading conclusions of the pharmacological analysis of the signal transduction pathways of gastric acid secretion, we evaluated various agents including inhibitors of protein kinase C, cyclic AMP-dependent protein kinase, phospholipase C, phospholipase A2, lipoxygenase, casein kinase, calmodulin, myosin light chain kinase, tyrosine kinase, anion exchanger, and protein phosphatase; and activators of protein kinase C. Among them, the cyclic AMP-dependent protein kinase inhibitor N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinylsulfonamide (H-89), the phospholipase A2 inhibitor 2-(p-amylcinnamoyl)amino-4-chlorobenzoic acid (ONO-RS-082), three myosin light chain kinase inhibitors (1-(5-iodonaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML-7), 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML-9), and wortmannin), the anion exchanger inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), the phospholipase C inhibitor neomycin, and most known calmodulin antagonists strongly inhibited [14C]aminopyrine accumulation, an indicator of acid secretion, in isolated rabbit gastric glands stimulated by N6,2'-O-dibutyryl-cyclic AMP. ONO-RS-082, calmidazolium, and DIDS inhibited H+,K+-ATPase. Most of the chemicals with antisecretory activity showed protonophore-like activity in gastric microsomes as well as in the mitochondria. It is concluded that H-89, ONO-RS-082, ML-7, ML-9, neomycin, and all calmodulin antagonists tested so far should not be used as tools to analyze gastric acid secretion.
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PMID:Nonspecific effects of the pharmacological probes commonly used to analyze signal transduction in rabbit parietal cells. 998 26