Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TRH stimulates a biphasic increase in intracellular free calcium ion, [Ca2+]i. Cells stably transfected with TRH receptor cDNA were used to compare the response in lines with and without L type voltage-gated calcium channels. Rat pituitary GH-Y cells that do not normally express TRH receptors, rat glial C6 cells, and human epithelial Hela cells were transfected with mouse TRH receptor cDNA. All lines bound similar amounts of [3H][N3-Me-His2]TRH with identical affinities (dissociation constant = 1.5 nM). Both pituitary lines expressed L type voltage-gated calcium channels; depolarization with high K+ increased 45Ca2+ uptake 20- to 25-fold and [Ca2+]i 12- to 14-fold. C6 and Hela cells, in contrast, appeared to have no L channel activity. GH4C1 cells responded to TRH with a calcium spike (6-fold) followed by a sustained second phase. When TRH was added after 100 nM nimodipine, an L channel blocker, the initial calcium burst was unaffected but the second phase was abolished. GH-Y cells transfected with TRH receptor cDNA responded to TRH with a 6-fold [Ca2+]i spike followed by a plateau phase (>8 min) in which [Ca2+]i remained elevated or increased. Nimodipine did not alter the peak TRH response or resting [Ca2+]i but reduced the sustained phase, which was eliminated by chelation of extracellular Ca2+. In the transfected glial C6 and Hela cells without calcium channels, TRH evoked transient, monophasic 7- to 9-fold increases in [Ca2+]i, and [Ca2+]i returned to resting levels within 3 min. Thapsigargin stimulated a gradual, large increase in [Ca2+]i in transfected C6 cells, and subsequent addition of TRH caused no further rise. Removal of extracellular Ca2+ from transfected C6 cells shortened the [Ca2+]i responses to TRH, to endothelin 1, and to thapsigargin. The TRH responses were pertussis toxin-insensitive. In summary, TRH can generate a calcium spike in pituitary, C6, and Hela cells transfected with TRH receptor cDNA, but the plateau phase of the [Ca2+]i response is not observed when the receptor is expressed in a cell line without L channel activity.
 ...
PMID:Characterization of the calcium response to thyrotropin-releasing hormone (TRH) in cells transfected with TRH receptor complementary DNA: importance of voltage-sensitive calcium channels. 127 82

Mitogen-activated protein (MAP) kinases are regarded as switch kinases in the phosphorylation cascade initiated by various agonists. We have investigated whether endothelins (ET), which are constrictor and mitogenic isopeptides, can increase MAP kinase activity in rat mesangial cells, using bovine myelin basic protein (MBP) as a substrate for an in vitro kinase assay. Treatment of quiescent mesangial cells with ET-1 rapidly stimulated a kinase activity which phosphorylated exogenous MBP. This stimulation was dose-dependent, with threshold responses at 1 nM-ET-1. Epidermal growth factor and thrombin also activated this kinase in mesangial cells. We also examined the ET signal transduction pathways leading to activation of MBP kinase. Pertussis toxin had no effect on ET-stimulated MBP kinase activity. Stimulation of protein kinase C by phorbol ester increased MBP kinase activity, and down-regulation of PKC partially inhibited ET-stimulated MBP kinase as well as phorbol ester-stimulated MBP kinase activity. Interestingly, genestein, an inhibitor of protein tyrosine kinases, partially inhibited MBP kinase stimulated by ET but not by phorbol esters. These results suggest that ET stimulates MBP kinase activity in rat mesangial cells via at least two pathways: one which is protein kinase C-dependent and a second one that involves a protein tyrosine kinase. Finally, by raising rabbit antibodies against the two forms of MAP kinase, p44mapk and p42mapk, we demonstrated that both isoforms are expressed in mesangial cells. Antibody alpha 1 Cp42 specifically immunoprecipitated p42mapk and allowed us to demonstrate that ET stimulates MBP kinase activity in the p42mapk immunocomplex. In conclusion, we have provided evidence that, in rat mesangial cells, MAP kinases are rapidly activated by ET-1, a regulatory process that involves at least protein kinase C activation and also a contribution of a tyrosine kinase not yet characterized.
 ...
PMID:Endothelin rapidly stimulates mitogen-activated protein kinase activity in rat mesangial cells. 128 Jan 3

In permeabilized C6 glioma cells and NIH 3T3 cells, the peptide endothelin 1 (ET-1) in combination with GTP gamma S stimulates the formation of inositol phosphates. In the presence of 10 microM GTP gamma S, ET-1 induces the formation of inositol phosphates with an EC50 value of 2.5 nM for C6 glioma cells and 1.6 nM for NIH 3T3 cells. The analogous peptide endothelin 3 (ET-3) is less potent than ET-1 in such action. In NIH 3T3 cells, ET-1+GTP gamma S-induced formation of inositol phosphates could be detected after 1 min of stimulation, and it increased for up to 30 min. ET-1-induced effects were partially reduced by pretreatment of the cells with pertussis toxin (1 microgram/ml) in C6 glioma cells, but were unaffected in NIH 3T3 cells. In binding studies in whole C6 cells and NIH 3T3 cells, specific binding for [125I]ET-1 was detected. Cross-linking of [125I]ET-1 in whole C6 cells revealed the presence of two binding proteins for ET-1 of 74 kDa and 55 kDa. ET-1 at 100 nM inhibited the labeling of both proteins by [125I]ET-1. However, ET-3 inhibited the labeling of the 55 kDa protein only. The results provide direct evidence for endothelin receptor coupling to phospholipase C through guanine nucleotide binding (G) proteins. In addition, in C6 cells, endothelin-mediated phospholipase C activation is partially inhibited by pertussis toxin pretreatment. The endothelin receptor involved in phospholipase C stimulation in C6 cells seems to correspond to a 74 kDa protein which binds ET-1 but not ET-3.
 ...
PMID:Endothelin-elicited stimulation of phospholipase C is mediated by guanine nucleotide binding protein(s). 132 77

Human breast cancer cells have been recently reported to produce endothelin (ET) 1. To investigate the potential regulation of ET production in breast cancer cells, we have measured the release of ET-like immunoreactivity from the T47D cell line in response to various paracrine/endocrine factors. Bombesin (0.1 microM) and cortisol (1 microM) stimulated maximal respective increases in IR-ET release to 580 and 369% of basal values after 6 h. The responses to cortisol and bombesin were additive. The response to bombesin was dose dependent with a median effective dose around 1 nM and was inhibited by the receptor antagonist [Leu13-psi-CH2NH-Leu14]bombesin. Pretreatment of T47D cells with pertussis toxin had no effect on bombesin-induced inositol lipid hydrolysis but inhibited ET-like immunoreactivity release in response to bombesin in the presence of glucocorticoid, by 56%. ET-1 (10 nM) and insulin-like growth factor (10 ng/ml) stimulated modest separate increases in DNA synthesis in human breast fibroblasts of 35 and 71%, respectively, but together exhibited a strong synergistic response to 905% of control values. This in vitro study demonstrates the potential for bombesin and glucocorticoid to regulate ET production in human breast cancer cells, which may in turn have a paracrine influence on neighboring stromal cell function.
 ...
PMID:Bombesin and glucocorticoids stimulate human breast cancer cells to produce endothelin, a paracrine mitogen for breast stromal cells. 155 Nov 9

Endothelin (ET)-1, -2, -3, big ET-1 and sarafotoxin S6b (S6b) dose-dependently increased phosphoinositide (PI) hydrolysis by 6- to 10-fold in cultured cerebellar granule cells prelabeled with [3H] myoinositol. The PI response elicited by ET-1 was dependent on the presence of extracellular Ca++, but was not reduced by organic (nisoldipine, nimodipine) or inorganic (Co++, Mn++) calcium channel blockers. Pretreatment of granule cells with tetrodotoxin or amiloride failed to affect the response to ET-1. Extracellular sodium depletion resulted in a marked increase in basal PI turnover; however, the net increase of PI turnover induced by ET-1 was unchanged. ET-induced PI breakdown could be partially inhibited by short or long term treatment with phorbol dibutyrate but was unaffected by pertussis toxin. ET- and S6b-induced PI turnover were dependent on the culturing time of granule cells, with the maximal response in a 4-day culture. The ET- and S6b-induced PI turnover appeared to be additive to that induced by carbachol, histamine, norepinephrine, serotonin, glutamate and maitotoxin. However, the responses induced by ET and S6b were nonadditive. Prestimulation of cells with ET or S6b for 30 sec to 24 hr resulted in dramatic loss of the ability of ET and S6b to stimulate PI hydrolysis, without affecting subsequent responsiveness induced by other stimuli, indicating homologous desensitization for ET- and S6b-induced responses. Moreover, our results further support the notion that ET and S6b act on the same population of receptors in cerebellar granule cells.
 ...
PMID:Endothelin- and sarafotoxin-induced phosphoinositide hydrolysis in cultured cerebellar granule cells: biochemical and pharmacological characterization. 164 18

We have previously demonstrated that human bronchial smooth muscle cells possess a single class of high-affinity binding sites for endothelin 1. In this study, we further characterized the receptor for endothelin 1 and evaluated the signal transduction mechanisms of this peptide. Stimulation of cultured human bronchial smooth muscle cells with endothelin 1 induced mobilization of Ca2+ from both intracellular and extracellular pools with a biphasic increase in cytoplasmic free Ca2+ concentration. Endothelin 1 increased cellular levels of inositol phosphates and diacylglycerol, indicating activation of phospholipase C, but induced production of inositol phosphates in smooth muscle cell membranes only in the presence of guanosine 5'-O-(thiotriphosphate) (GTP gamma S). Treatment of smooth muscle cells with pertussis toxin failed to block the endothelin 1-induced increase in inositol phosphate production and Ca2+ mobilization. These results suggest that the receptor for endothelin 1 in bronchial smooth muscle is coupled to phospholipase C through a pertussis toxin-insensitive G protein. Affinity crosslinking experiments identified the endothelin 1 receptor as a single band with an apparent molecular weight of approximately 70,000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis, further supporting the functional evidence that endothelin 1 receptor belongs to the G protein-linked rhodopsin type of receptor superfamily.
 ...
PMID:Mechanisms of calcium mobilization and phosphoinositide hydrolysis in human bronchial smooth muscle cells by endothelin 1. 165 61

Both human endothelin 1 (ET1) and rat endothelin 3 (ET3) produced dose-dependent pressor effects in the pithed rat. The pressor actions of ET3 and arginine vasopressin (AVP) were compared with one another in pithed rats in the presence of the calcium channel activator BAY K 8644 or the calcium channel antagonist nifedipine i.a. and also after pretreatment with pertussis toxin i.v. The diastolic pressure recorded in animals treated with the vehicle was 41 +/- 1 mm Hg, and administration of BAY K 8644 increased the diastolic pressure to 53 +/- 3 mm Hg, whereas nifedipine caused a decrease in diastolic pressure to 33 +/- 2 mm Hg. AVP, ET1 and ET3 dose-dependently increased diastolic blood pressure, with AVP being the most potent and producing the greatest total increase in pressure. ET1 was more potent than ET3; however, the maximal increases produced by the endothelins were identical. The actions of ET3 but not AVP were potentiated in the presence of BAY K 8644. Furthermore, nifedipine significantly impaired responses induced by endothelin but not those produced by AVP. It was observed that animals treated with pertussis toxin 3 days before the conduction of the experiments had a significantly lower diastolic blood pressure as compared with saline-treated animals. Treatment with pertussis toxin caused the dose-diastolic pressure response curve to ET to be displaced to the right, whereas the dose-diastolic pressure response to AVP was not affected.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Comparison between the vasoactive actions of endothelin and arginine vasopressin in pithed rats after pretreatment with BAY K 8644, nifedipine or pertussis toxin. 169 83

Endothelins (ETs) are a family of vasoactive peptides with profound biological actions in diverse cell systems. Among its varied actions, ET stimulates phospholipase C (PLC) in cultured mesangial cells. We investigated the presence of specific ET receptors in rat mesangial cells in culture, and studied the role of GTP-binding proteins (G proteins) in coupling PLC to the endothelin receptor. [125I]ET binding was time- and temperature-dependent, and Scatchard analysis of saturation data showed a single class of high-affinity binding sites. Heterologous displacement with two related peptides, ET-3 and sarafotoxin (SFTX), revealed the presence of two binding sites for these isopeptides. Preincubation of cells with ET-1 reduced the receptor number without affecting Kd, and this effect was not prevented by protein kinase C inhibition or downregulation. We confirmed the presence of a 41- to 43-kDa pertussis toxin substrate in rat mesangial cell membranes in an ADP ribosylation assay. ET-1 inhibits and GDP beta S enhances toxin-catalyzed transfer of ADP-ribose to this substrate. ET-1 potentiated GTP gamma S-induced phosphatidylinositol (PI) hydrolysis in a concentration-dependent manner. In addition, pertussis toxin partially inhibited ET-stimulated PI hydrolysis in intact mesangial cells. Pertussis toxin also reduced the magnitude of ET-stimulated intracellular free calcium [( Ca2+ )i]. Thus, ET-1 binds to specific receptors on rat mesangial cells and activates PLC, in part, through a pertussis toxin-sensitive G-protein.
 ...
PMID:Endothelin receptors and coupled GTP-binding proteins in glomerular mesangial cells. 172 39

Endothelin (ET)-related peptides robustly stimulated [3H]-inositol phosphate (IP) formation in cultured cerebellar granule cells, astrocytes, and C6 glioma cells. Their agonist selectivities were ET-1 = ET-2 greater than or equal to sarafotoxin S6b greater than ET-3 greater than big ET-1 for granule cells and ET-1 greater than or equal to ET-2 greater than or equal to S6b greater than big ET-1 greater than ET-3 for cerebellar astrocytes and C6 glioma cells. These effects were Ca(2+)-dependent but insensitive to antagonists of L-type Ca2+ channels and the Na+/Ca2+ antiporter. Pretreatment of cells with ET-1 or S6b induced homologous desensitization of phosphoinositide (PI) response mediated by ET receptors. Long-term pertussis toxin (PTX) treatment attenuated the phosphoinositide (PI) response in astrocytes and glioma but not in granule cells. ET-1 and its related peptides increased [Ca2+]i in C6 glioma by two distinct pathways: IP3-induced Ca2+ mobilization or receptor-operated Ca2+ influx. La3+, Mn2+, and Cd2+ inhibited the Ca2+ influx and sustained PI turnover, while Ca2+ mobilization was attenuated by phorbol ester and TMB-8. ET-induced Ca2+ influx was essential for the sustained [Ca2+]i increase and PI turnover. Homologous desensitization of [Ca2+]i increase was also noted. In cerebellar granule cells, ET evoked the release of [3H]D-aspartate from these neurons. This action appears to be dependent on PI hydrolysis and [Ca2+]i increase and modulated by protein kinase C.
 ...
PMID:Endothelin-induced activation of phosphoinositide turnover, calcium mobilization, and transmitter release in cultured neurons and neurally related cell types. 172 40

High-affinity specific receptors of endothelin (ET-1) were identified on primary cultures of mouse embryo striatal astrocytes by binding experiments performed with 125I-ET-1. Stimulation of production of inositol phosphates, a biphasic increase of the intracellular calcium concentration, and inhibition of cyclic AMP accumulation were observed in the same cells under ET-1 stimulation. Pretreatment of these cells with Bordetella pertussis toxin affected these effects to different extends, an observation suggesting that they are mediated by multiple transduction pathways, possibly involving several guanine nucleotide-binding proteins.
 ...
PMID:Are several G proteins involved in the different effects of endothelin-1 in mouse striatal astrocytes? 184 77


1 2 3 4 5 6 7 8 Next >>