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)

To examine whether the subpopulation of the rat type 1 angiotensin II (AII) receptor (AT1A) couples with a single or multiple signal transduction pathways, we constructed Chinese hamster ovary (CHO) cell lines producing the recombinant receptor. The expressed AT1A receptor exhibits typical pharmacological characteristics of the AT1 receptor, known to mediate the main physiological function of AII. Addition of AII to the CHO cells induced a rapid, transient increase in intracellular free Ca2+ concentrations ([Ca2+]i) followed by a lower, sustained phase. Nicardipine, a blocker of voltage-dependent L-type Ca2+ channels, attenuated the transient [Ca2+]i response and abolished the sustained phase. The transient phase was also reduced dose-dependently by the phospholipase C inhibitor neomycin. Furthermore, AII inhibited forskolin-evoked cAMP accumulation. These data suggest, although another subpopulation named AT1B is present, that the rat AT1A receptor can independently couple with all three signal transduction pathways known to be induced by AII: i.e., i) activation of phospholipase C resulting in InsP3 generation with a subsequent release of intracellularly stored Ca2+, ii) activation of dihydropyridine-sensitive voltage-dependent Ca2+ channels, and iii) inhibition of adenylate cyclase activity.
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PMID:The rat angiotensin II AT1A receptor couples with three different signal transduction pathways. 137 99

Cultured aortic smooth muscle cells from SHR proliferate more actively than cells normotensive control animals. This experimental data may be related to the hypertensive arteriopathy which mainly proceeds from media dystrophy made of hypertrophy, hyperplasia and excessive protein secretion of the smooth muscle cells. In order to precise the molecular cause of the phenomenon and the eventual action of calcium channel blockers on the development of this organic characteristic of hypertension, we have compared the responses of cultured cells from both SH and WKY rats to various agents in the absence or presence of verapamil. Cell proliferation, phospholipase C activation, and c-jun and c-fos oncogene expressions were measured in both cultures under the same conditions. The mitogenic actions of both foetal calf serum (FCS) and angiotensin II are two times more important on SH than on WKY rat cells. However, while inositol phosphate production elicited by angiotensin in also doubled in SHR cultures versus WKY ones. FCS-induced PLC activation is equivalent in both types of cells. The proto-oncogenes are more intensively expressed when WKY cells are stimulated by FCS than in the presence of angiotensin, but, contrarily to angiotensin, serum is not more active upon this parameter in SHR cultures. Verapamil (from 10(-8) M to 10(-5) M) decreases by 30% the proliferative effect of serum in both SH and WKY rat cells but is not significantly active on angiotensin stimulation. It also depresses in the same proportion the serum-induced inositol phosphate production and oncogene expressions without altering the responses to angiotensin. Nicardipine is less active than verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Role of external calcium on the growth of aortic smooth muscle cells in SHR]. 212 55

The effects of GABA on catecholamine release and phosphoinositide metabolism were studied in cultured bovine adrenal chromaffin cells. GABA and muscimol, a specific agonist for the GABAA receptor, each evoked a gradual secretion of catecholamines from the cells in the presence of ouabain, an inhibitor of Na+, K(+)-ATPase. This release was inhibited by bicuculline, a specific antagonist for the GABAA receptor, or by picrotoxin, a blocker of GABA-gated Cl- channels, and was potentiated by diazepam or pentobarbital. GABA or muscimol induced a concentration-dependent formation of inositol phosphates. This accumulation of inositol phosphates was also inhibited by bicuculline, picrotoxin or removal of extracellular Ca2+, and also potentiated by diazepam and pentobarbital. Nicardipine suppressed GABA-induced catecholamine release in the presence of ouabain and accumulation of inositol phosphates, while verapamil, diltiazem, and omega-conotoxin failed to inhibit these responses to GABA. The phosphoinositide-specific phospholipase C inhibitor neomycin also inhibited both GABA-induced accumulation of inositol phosphates and stimulation of catecholamine release in the presence of ouabain. These results taken together indicate that GABA evoked catecholamine release from the chromaffin cells in the presence of ouabain by stimulation of phosphoinositide metabolism in a Ca2(+)-sensitive manner via activation of GABAA receptor-coupled Cl- channels.
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PMID:Involvement of phosphoinositide metabolism in GABA-induced catecholamine release from cultured bovine adrenal chromaffin cells. 217 9

We investigated possible involvement of voltage-dependent Ca(2+) channels (VDCCs) and several intracellular signaling mechanisms in multiple actions of basic fibroblast growth factor (bFGF), such as survival promotion, induction of calbindin D(28k) expression as well as acceleration of neuritic branch formation of cultured rat hippocampal neurons. Immunocytochemical staining with anti-gamma-aminobutyric acid (GABA) antibody showed that the promotion of neuron survival by bFGF in high cell-density cultures were exerted exclusively on GABA-negative neurons. Nicardipine (5 microM) attenuated the effect of bFGF on neuronal survival and formation of neurite branches, suggesting that the activity of L-type VDCCs is required for these effects. In contrast, stimulation of calbindin expression by bFGF was not attenuated by nicardipine. A phospholipase C inhibitor U73122 (1 microM) prevented the effect of bFGF on neurite branch formation, but not on neuronal survival or calbindin expression. On the other hand, chronic application of phorbol-12-myristate-13-acetate (1 microM) inhibited the effect of bFGF on neuronal survival, without inhibiting the other bFGF actions. Forskolin (100 microM) attenuated the effect of bFGF on neuronal survival and neurite branch formation, indicating that cyclic AMP plays negative regulatory roles in these actions of bFGF. Taken together, these results suggest that multiple biological actions of bFGF on hippocampal neurons are exerted through, and modulated by, distinct signaling pathways.
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PMID:Distinct signaling pathways involved in multiple effects of basic fibroblast growth factor on cultured rat hippocampal neurons. 1110 78

The effect of the muscarinic receptors agonist carbachol (Cch) on intracellular calcium concentration ([Ca(2+)](i)) and cAMP level was studied in polarized Fischer rat thyroid (FRT) epithelial cells. Cch provoked a transient increase in [Ca(2+)](i), followed by a lower sustained phase. Thapsigargin, a specific microsomal Ca(2+)-ATPase inhibitor, caused a rapid rise in [Ca(2+)](i) and subsequent addition of Cch was without effect. Removal of extracellular Ca(2+) reduced the initial transient response and completely abolished the plateau phase. Ryanodine, an agent that depletes intracellular Ca(2+) stores through stimulation of ryanodine receptors (RyRs), had no effect on [Ca(2+)](i). However, the transitory activation of [Ca(2+)](i) was dose-dependently attenuated in cells pretreated with U73122, a specific inhibitor of phospholipase C (PLC). These data suggest that the Cch-stimulated increment of [Ca(2+)](i) required IP(3) formation and binding to its specific receptors in Ca(2+) stores. Further studies were performed to investigate whether the effect of Cch on Ca(2+) entry into FRT cells was via L-type voltage-dependent Ca(2+) channels (L-VDCCs). Nicardipine, a nonspecific L-type Ca(2+) channel blocker, decreased Cch-induced increase on [Ca(2+)](i), while Bay K-8644, an L-type Ca(2+) channel agonist, slightly increased [Ca(2+)](i) in FRT cells. These data indicate that Ca(2+) entry into these nondifferentiated thyroid cells occurs through an L-VDCC, and probably through another mechanism such as a capacitative pathway. Cch did not affect the intracellular cAMP levels, but its effects on [Ca(2+)](i) were significantly reduced when cells were pretreated with forskolin, suggesting the existence of an intracellular cross-talk between PLC and cAMP mechanisms in the regulation of intracellular Ca(2+) mobilization in neoplastic FRT cells.
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PMID:Activation of muscarinic acetylcholine receptors induces Ca(2+) mobilization in FRT cells. 1128 59