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)

WISH cells grown in vitro were pretreated with subcytotoxic concentrations of digitonin, cortisol and purified bacterial toxins -- staphylococcal beta-haemolysin or Clostridium perfringens alpha-toxin and irradiated with 3 GHz electromagnetic wave (microwaves) at the field power densities 5 or 40 mW/cm2. At 40 mW/cm2 increase in temperature of the culture medium of about 2-3 degrees C was noted, while at 5 mW/cm2 no detectable increase in temperature was found. Control and pretreated WISH cells after irradiation in the microwave field were used for evaluation of their viability, incorporation of tritiated thymidine, glycine and uridine and level of intracellular cyclic AMP. Irradiation with microwaves resulted in lowering of thymidine and glycine incorporation along with changes in the intracellular amount of cAMP (decrease in cells exposed to 5 mW/cm2 and increase in those exposed to 40 mW/cm2). Under both conditions viability of the cultures was normal. Pretreatment of cells with digitonin or purified bacterial toxins followed by irradiation with microwaves resulted in enhancement of the cytotoxic effect with lowering of cell viability, especially after exposition to power density of 40 mW/cm2. Cortisol led to decrease in 3H-glycine and 3H-uridine incorporation into WISH cells, but did not influence the reaction of the cells to microwave radiation. In view of the results presented it may be concluded that substances injuring cell membranes sensitize cell cultures to electromagnetic radiation of the microwave range and may enhance the specific (non-thermal) effect of microwaves.
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PMID:Effect of microwave radiation on cells treated with membrane-injuring substances. 20 Apr 52

We have examined the effects of hydrocortisone on growth and Na+/H+ exchange in cultured rat aortic vascular smooth muscle cells (VSMC). Hydrocortisone (2 microM) treatment of growth-arrested VSMC significantly decreased VSMC growth in response to 10% calf serum assayed by 3H-thymidine incorporation and cell number at confluence. This effect was associated with the appearance of an altered cell phenotype characterized by large, flat VSMC that did not form typical "hillocks." Na+/H+ exchange was also altered in hydrocortisone-treated cells assayed by dimethylamiloride-sensitive 22Na+ influx into acid-loaded cells or by intracellular pH (pHi) change using the fluorescent dye BCECF. Resting pHi was 7.25 +/- 0.04 and 7.15 +/- 0.05 in control and hydrocortisone-treated cells, respectively (0.1 less than P less than 0.05). Following intracellular acidification in the absence of external Na+, pHi recovery upon addition of Na+ was increased 89% in hydrocortisone-treated cells relative to control. This was due to an increase in the Vmax for the Na+/H+ exchanger from 17.5 +/- 2.4 to 25.9 +/- 2.0 nmol Na+/mg protein x min (P less than 0.01) without a significant change in Km. Treatment of VSMC with actinomycin D (1 microgram/ml) or cycloheximide (10 microM) completely inhibited the hydrocortisone-mediated increase in Na+/H+ exchange, indicating a requirement for both RNA and protein synthesis. Because hydrocortisone altered the Vmax for Na+/H+ exchange, in contrast to agonists such as serum or angiotensin II which alter the Km for intracellular H+ or extracellular Na+, respectively, we studied the effect of hydrocortisone on activation of Na+/H+ exchange by these agonists. In cells maintained at physiological pHi (7.2), the initial rate (2 min) of angiotensin II-stimulated alkalinization was increased 66 +/- 39% in hydrocortisone-treated compared with control cells. Hydrocortisone caused no change in angiotensin II-stimulated phospholipase C activity assayed by measurement of changes in intracellular Ca2+ or diacylglycerol formation. However, angiotensin II and serum stimulated only small increases in Na+/H+ exchange in acid-loaded (pHi = 6.8) hydrocortisone-treated cells. These findings suggest that hydrocortisone-mediated increases in VSMC Na+/H+ exchange occur in association with a nonproliferating phenotype that has altered regulation of Na+/H+ exchange activation. We propose that hydrocortisone-mediated growth inhibition may be a useful model for studying the role of Na+/H+ exchange in cell growth responsiveness.
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PMID:Effects of glucocorticoids on Na+/H+ exchange and growth in cultured vascular smooth muscle cells. 246 79

Progesterone at concentrations of 10(-7)M and 10(-8)M inhibits release of [3H]-arachidonic acid from stimulated, perfused, endometrial cells. The effect is independent of the mechanism of stimulation. Cortisol (10(-5)M but not 10(-7)M) has a similar effect in this system but estradiol (10(-7)M) is without effect. There was a positive correlation (p less than 0.05) between the magnitude of inhibition by progesterone and the day of cycle. The inhibitory action of progesterone on the release of arachidonic acid was greater in endometrial cells than in decidual cells and was apparent after fifteen minutes. The activities of commercial and endometrial cell-free preparations of phospholipase A2 and phospholipase C were unaffected by the presence of progesterone. We conclude that progesterone modulates release of [3H]-arachidonic acid from endometrial cells by a rapid, indirect action on phospholipase activity.
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PMID:The effect of progesterone on the release of arachidonic acid from human endometrial cells stimulated by histamine. 308 83

Increasing evidence has accumulated for rapid nongenomic steroid actions in various cell systems and, more recently, for rapid aldosterone effects on the Na(+)-H+ antiport in human mononuclear leukocytes. The aim of the present study was to demonstrate a rapid, nongenomic aldosterone action in rat vascular smooth muscle cells as a key effector cell in cardiovascular regulation. Basal 22Na+ influx in quiescent vascular smooth muscle cells was 22.1 +/- 1.9 nmol/mg protein per minute (mean +/- SEM, n = 9). Aldosterone (1 nmol/L) stimulated influx to 28.6 +/- 1.5 nmol/mg protein per minute after 4 minutes (n = 9, P < .05), with a half-maximal effect between 0.1 and 0.5 nmol/L; the effects were inhibited by ethylisopropylamiloride, the specific inhibitor of the Na(+)-H+ exchanger, demonstrating the involvement of this transport system in rapid effects of aldosterone. Hydrocortisone (1 mumol/L) was ineffective, and fludrocortisone and deoxycorticosterone increased influx with half-maximal effects at approximately 0.5 nmol/L. Canrenone, a classic antagonist of aldosterone action, did not inhibit stimulation by aldosterone at a 1000-fold excess concentration. Aldosterone significantly stimulated intracellular inositol 1,4,5-trisphosphate levels (P < .05) after 30 seconds; the inhibitors of phospholipase C, neomycin and U-73122, inhibited aldosterone-stimulated Na+ influx and increase of intracellular inositol 1,4,5-trisphosphate. The rapid stimulation of sodium transport in vascular smooth muscle cells and the pharmacological characteristics of this effect are clearly incompatible with the classic, genomic pathway of steroid action and represent further evidence for nongenomic effects of aldosterone.
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PMID:Rapid effects of aldosterone on sodium transport in vascular smooth muscle cells. 784 42

Cultures of enzymatically dispersed porcine anterior pituitary cells were used to examine the effects of cortisol on luteinizing hormone secretion induced by a variety of compounds which activate different intracellular signal transduction mechanisms. Cells were pre-incubated with or without cortisol (200 micrograms/ml) for 3 days, washed and then incubated for 4 h with or without cortisol in the presence or absence of these compounds. Luteinizing hormone in the media was assayed by radioimmunoassay. Cortisol treatment had no effect on basal luteinizing hormone release, but reduced gonadotropin-releasing hormone (8.5 x 10(-8) mol/l) stimulated luteinizing hormone secretion. Phospholipase C, 8-bromo-cyclic adenosine 3',5'-monophosphate, and 12-O-tetradecanoyl-phorbol-13-acetate (an activator of protein kinase C) all stimulated luteinizing hormone secretion in a dose-dependent manner in cortisol-untreated cells. Pretreatment with cortisol inhibited luteinizing hormone secretion induced by phospholipase C and 8-bromo-cyclic adenosine 3',5'-monophosphate, but did not affect the secretion of luteinizing hormone in response to 12-O-tetradecanoyl-phorbol-13 acetate. Cortisol inhibited GnRH-induced inositol phosphate production. Our results suggest that the inhibitory action of cortisol on stimulus-coupled luteinizing hormone secretion may be exerted at two different intracellular sites: (1) by inhibition of phospholipase C activity and (2) at a point distal to cyclic adenosine 3',5'-monophosphate generation.
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PMID:Modulation by cortisol of luteinizing hormone secretion from cultured porcine anterior pituitary cells: effects on secretion induced by phospholipase C, phorbol ester and cAMP. 813 98

While the mechanisms governing genomically mediated glucocorticoid actions are becoming increasingly understood, relatively little is known with regard to the cell signaling pathways that transduce rapid glucocorticoid actions. Studies of the cultured tilapia rostral pars distalis (RPD), a naturally segregated region of the fish pituitary gland that contains a 95-99% pure population of prolactin (PRL) cells and is easily dissected and maintained in a completely defined, serum-free media, indicate that physiological concentrations of cortisol rapidly inhibit PRL release. The attenuative action of cortisol on PRL release occurs within 10-20 min, is insensitive to the protein synthesis inhibitor, cycloheximide, and mimicked by its membrane impermeable analog, cortisol-21 hemisuccinate-conjugated bovine serum albumin (BSA). Cortisol and somatostatin, a peptide known to work through membrane receptors to inhibit PRL release, rapidly and reversibly reduces intracellular free Ca(2+) (Ca(i)(2+)), and inhibits 45Ca(2+) influx and BAYK-8644 induced PRL release. Preliminary investigations show cortisol, but not somatostatin, suppresses phospholipase C (PLC) activity in PRL cell membrane preparations. In addition, cortisol and somatostatin reduce intracellular cAMP and membrane adenylyl cyclase activity. These findings indicate that the acute inhibitory effects of cortisol on PRL release occur through a nongenomic mechanism involving interactions with the plasma membrane and inhibition of both the Ca(2+) and cAMP signal transduction pathways. Cortisol may reduce Ca(i)(2+) by inhibiting influx through L-type voltage-gated channels and possibly release through a PLC/inositol triphosphate sensitive intracellular Ca(2+) pool. In addition, it is also likely the steroid inhibits adenylyl cyclase activity in events leading to reduced cAMP production and the subsequent release of PRL.
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PMID:Signal transduction mechanisms mediating rapid, nongenomic effects of cortisol on prolactin release. 1196 Jun 33

Neuropeptides B and W (NPB and NPW) are regulatory peptides that act via two subtypes of G protein-coupled receptors, named GPR7 and GPR8. RT-PCR demonstrated the expression of these receptors in both zona glomerulosa and zona fasciculata-reticularis (ZF/R) cells of the human adrenal cortex. NPB and NPW did not affect aldosterone secretion from dispersed zona glomerulosa cells but enhanced cortisol production from ZF/R cells, NPB being more effective than NPW. NPB evoked sizable cAMP and inositol triphosphate responses from ZF/R cells, which were abrogated by the adenylate cyclase inhibitor SQ-22536 and the phospholipase C inhibitor U-73122, respectively. Cortisol response to NPB was lowered by either SQ-22536 and the protein kinase (PK) A inhibitor H-89 or U-73122 and the PKC inhibitor calphostin-C and abolished by the simultaneous exposure to H-89 and calphostin-C. NPW elicited only a rise in cAMP production from dispersed ZF/R cells, and its cortisol response was suppressed by both SQ-22536 and H-89. PreproNPB and preproNPW mRNAs were detected in human adrenal cortexes. We conclude that: 1) NPB and NPW exert a secretagogue action on human ZF/R cells, probably acting in an autocrine-paracrine manner; and 2) the effect of NPB is mediated by both the adenylate cyclase/PKA and the phospholipase C/PKC cascades, whereas that of NPW involves only the activation of the former signaling pathway.
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PMID:G protein receptors 7 and 8 are expressed in human adrenocortical cells, and their endogenous ligands neuropeptides B and w enhance cortisol secretion by activating adenylate cyclase- and phospholipase C-dependent signaling cascades. 1579 61