UMLS:C0043167 - FACTA Search

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)

Previous studies have suggested that activation of D2-like dopamine receptors inhibits catecholamine secretion from adrenal chromaffin cells. The purpose of this study was to determine whether the activation of D1-like receptors on chromaffin cells affects either catecholamine release from the cells or the inhibition of secretion by D2-like dopamine receptors. Both D1- and D2-selective agonists inhibited secretion elicited by dimethylphenylpiperazinium (DMPP), veratridine, and high K+ levels. The D1-selective agonists 6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5- tetrahydro-1H-3-benzazepine (CI-APB) and SKF-38393 inhibited DMPP-stimulated catecholamine secretion in a concentration-dependent manner; 50% inhibition was obtained with approximately 10 microM CI-APB and approximately 100 microM SKF-38393. Of the D2-selective agonists, bromocriptine was a more potent inhibitor of DMPP-stimulated catecholamine release than was quinpirole. The inhibition of secretion caused by CI-APB or SKF-38393 was additive with the inhibition caused by bromocriptine. Pertussis toxin treatment (50 ng/ml, 18 h) attenuated the inhibitory effect of D2-selective, but not D1-selective, dopamine agonists. In addition, forskolin-stimulated adenylyl cyclase activity was inhibited by D2-selective, but not D1-selective, agonists. Neither D1- nor D2-selective agonists stimulated adenylyl cyclase activity in the cells, although cyclase activity was stimulated by forskolin, carbachol, and vasoactive intestinal peptide. DMPP-stimulated Ca2+ uptake was inhibited by both D1- and D2-selective dopamine agonists. PCR analysis was used to determine which of the dopamine receptor subtypes within the D1-like and D2-like subfamilies was responsible for the observed inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Dopaminergic inhibition of catecholamine secretion from chromaffin cells: evidence that inhibition is mediated by D4 and D5 dopamine receptors. 852 58

Sphingolipids have been proposed to modulate cell function by acting as intracellular second messengers and through binding to plasma membrane receptors. Exposure of MC3T3-E1 osteoblastic cells to sphingosine (SPH), sphingosine-1-phosphate (SPP), or sphingosylphosphorylcholine (SPC) led to the release of Ca2+ from the endoplasmic reticulum (ER) and acute elevations in cytosolic-free Ca2+ ([Ca2+]i). Desensitization studies suggest that SPP and SPC bind plasma membrane endothelial differentiation gene (Edg) receptors for lysophosphatidic acid (LPA). Consistent with the coupling of Edg receptors to G proteins, SPP- and SPC-induced Ca2+ signaling was inhibited by pretreatment of the cells with pertussis toxin (PTx). Of the Edg receptors known to bind SPH derivatives in other cell types, MC3T3-E1 cells were found to express transcripts encoding Edg-1 and Edg-5 but not Edg-3, Edg-6, or Edg-8. In contrast to SPP and SPC, the ability of SPH to elicit [Ca2+]i elevations was affected neither by prior exposure of cells to LPA nor by PTx treatment. However, LPA-induced Ca2+ signaling was blocked in MC3T3-E1 cells previously exposed to SPH. Elevations in [Ca2+]i were not evoked by SPP or SPC in cells treated with 2-aminoethoxydiphenylborate (2-APB), an inhibitor of inositol 1,4,5-trisphosphate (IP3)-gated Ca2+ channels in the ER. No effect of 2-APB was observed on SPH-or LPA-induced [Ca2+]i elevations. The data support a model in which SPP and SPC bind Edg-1 and/or Edg-5 receptors in osteoblasts leading to the release of Ca2+ from the ER through IP3-gated channels.
...
PMID:A role for G protein-coupled lysophospholipid receptors in sphingolipid-induced Ca2+ signaling in MC3T3-E1 osteoblastic cells. 1169 99

In vitro experiments were performed to investigate the actions of endothelin-1 (ET-1) on vasomotion and vasospasm in guinea-pig mesenteric lymphatics. ET-1 modulated lymphatic vasomotion independent of the endothelium, with lower concentrations (<or=10 nm) increasing lymphatic vasomotion and higher concentrations (>or=100 nm) causing vasospasm. ET-1-induced increases in vasomotion were accompanied by an increase in tonic [Ca2+]i. These actions were inhibited by the ETA receptor antagonist BQ-123 (1 microm), the phospholipase C (PLC) inhibitor U73122 (5 microm), removal of extracellular Ca2+, chelation of intracellular Ca2+ with BAPTA/AM (10 microm), the store Ca2+-ATPase inhibitor thapsigargin (1 microm), caffeine (10 mm) and the inositol 1,4,5-trisphosphate (IP3) receptor blocker heparin and 2-APB (30 microm). In contrast, the ETB receptor antagonist BQ-788 (1 microm), ryanodine (1 & 20 microm), pertussis toxin (PTx) or Cs+ had no significant actions on vasomotion or the magnitude of increase in tonic [Ca2+]i. ET-1-induced vasospasm was accompanied by a transient increase in smooth muscle [Ca2+]i followed by a sustained plateau, an action that was abolished by removal of extracellular Ca2+, but only marginally inhibited by nifedipine (1 microm). Caffeine (10 mm), SKF 96165 (30 microm) or U73122 (5 microm) together with nifedipine (1 microm) abolished ET-1-induced vasospasm and increase in [Ca2+]i. These results indicate that ET-1 increases lymphatic vasomotion by acting on smooth muscle ETA receptors and activation of G-protein-PLC-IP3 cascade, which is known to cause pacemaker Ca2+ release and resultant pacemaker potentials. High concentrations of ET-1 cause a failure in Ca2+ homeostasis causing vasospasm, triggered by excessive Ca2+ influx primarily through store-operated channels (SOCs) with l-Ca2+ voltage-operated channels (VOCs) also contributing, but to a much lesser extent.
...
PMID:ET-1-associated vasomotion and vasospasm in lymphatic vessels of the guinea-pig mesentery. 1462 68

Protease-activated receptors (PARs) are a group of four members of the superfamily of G protein-coupled receptors that transduce cell signaling by proteolytic activity of extracellular serine proteases, such as thrombin. Possible expression and functions of PARs in oligodendrocytes, the myelin forming cells of the CNS, are still unclear. Here, the oligodendrocyte cell line OLN-93 was used to investigate the signaling of PARs. By reverse transcription-polymerase chain reaction (RT-PCR), immunostaining and Ca(2+) imaging studies, we demonstrate that OLN-93 cells functionally express PAR-1. PAR-3 seems to be expressed without apparent activity, and PAR-2 and PAR-4 cannot be detected. Short-term stimulation of the OLN-93 cells with PAR-1 agonists, such as thrombin, trypsin and PAR-1 activating peptide, dose-dependently induced a transient rise of [Ca(2+)](i). Concentration-effect curves display a sigmoidal concentration dependence. Elevation of [Ca(2+)](i) induced by PAR-1 mainly resulted from Ca(2+) release from intracellular stores. Studies on the effects of pertussis toxin (PTX), phospholipase C antagonist and 2-APB, showed that in OLN-93 cells (i). the calcium signaling cascade from PAR-1 was mediated through PTX-insensitive G proteins, (ii). activation of phospholipase C and liberation of InsP(3) were events upstream of the Ca(2+) release from the stores. In addition, the present study analyzed PAR-1 desensitization caused by exposure to thrombin, trypsin, and PAR-1 activating peptide, elucidated the influence of the protease cathepsin G on PAR-1 activation, and also characterized PAR-1 desensitization. This is the first study, which shows that OLN-93 oligodendrocytes functionally express PAR-1, and identifies the receptor coupling to mobilization of intracellular calcium. Moreover, the expression of PAR-1 was demonstrated by RT-PCR in primary oligodendrocytes from rat brain.
...
PMID:Expression of protease-activated receptors (PARs) in OLN-93 oligodendroglial cells and mechanism of PAR-1-induced calcium signaling. 1514 74

A polyclonal antibody (APP-Ab) raised against the extracellular domain of the beta-amyloid precursor protein (APP) triggers a marked neuronal cell death preceded by activation of Ca(2+)-dependent enzymes, neurite degeneration, oxidative stress and nuclear condensation [Mbebi et al. (2002) J. Biol. Chem., 277, 20979-20990]. We have investigated whether activation of APP by this antibody could promote cell death through cellular Ca2+ homeostasis alteration. We carried out time-lapse recordings of intracellular Ca2+ signals in cultured mice cortical neurons by means of a scanning confocal microscope. When applied in the presence of 2 mm external Ca2+, APP-Ab elicited a long-lasting elevation of the intracellular concentration of Ca2+ ([Ca2+]i). Experiments performed in the absence of external Ca2+ showed that APP-Ab triggers the release of Ca2+ from intracellular stores. The re-admission of external Ca2+ provides an additional rise of Ca2+ most likely through store-operated channels. A pretreatment of the cells with pertussis toxin, to inhibit the activity of Gi/Go proteins, or with the phospholipase C inhibitor, 3-nitrocoumarin, prevented both the APP-dependent elevation of Ca2+ as well as the APP-Ab-mediated cell death. Similarly, the store-operated channel inhibitors, 2-APB or SKF-96365 block both the APP-Ab-dependent Ca2+ entry and the APP-Ab-mediated cell death. Altogether, our data provide functional evidence that APP can perturb intracellular Ca2+ homeostasis by emptying intracellular Ca2+ stores and triggering Ca2+ entry through store-operated channels. In response to APP activation, the long-lasting elevation of [Ca2+]i due to an entry of Ca2+ via store-operated channels appears as a major event that leads to neuronal cell death.
...
PMID:The beta-amyloid precursor protein controls a store-operated Ca2+ entry in cortical neurons. 1545 86

This study determined the effects of alpha1-adrenergic receptor (alpha1-AR) stimulation by phenylephrine (PE) on L-type Ca2+ current (I(Ca,L)) in cat atrial myocytes. PE (10 microm) reversibly increased I(Ca,L) (51.3%; n = 40) and shifted peak I(Ca,L) activation voltage by -10 mV. PE-induced stimulation of I(Ca,L) was blocked by each of 1 microm prazocin, 10 microm L-NIO, 10 microm W-7, 10 microm ODQ, 2 microm H-89 or 10 microm LY294002, and was unaffected by 10 microm chelerythrine or incubating cells in pertussis toxin (PTX). PE-induced stimulation of I(Ca,L) also was inhibited by each of 10 microm ryanodine or 5 microm thapsigargin, by blocking IP3 receptors with 2 microm 2-APB or 10 microm xestospongin C or by intracellular dialysis of heparin. In field-stimulated cells, PE increased intracellular NO (NOi) production. PE-induced NOi release was inhibited by each of 1 microm prazocin, 10 microm L-NIO, 10 microm W-7, 10 microm LY294002, 2 microm H-89, 10 microm ryanodine, 5 microm thapsigargin, 2 microm 2-APB or 10 microm xestospongin C, and unchanged by PTX. PE (10 microm) increased phosphorylation of Akt, which was inhibited by LY294002. Confocal microscopy showed that PE stimulated NOi release from subsarcolemmal sites and this was prevented by 2 mm methyl-beta-cyclodextrin, an agent that disrupts caveolae formation. PE also increased local, subsarcolemmal SR Ca2+ release via IP3-dependent signalling. Electron micrographs of atrial myocytes show peripheral SR cisternae in close proximity to clusters of caveolae. We conclude that in cat atrial myocytes PE acts via alpha1-ARs coupled to PTX-insensitive G-protein to release NOi, which in turn stimulates I(Ca,L). PE-induced NOi release requires stimulation of both PI-3K/Akt and IP3-dependent Ca2+ signalling. NO stimulates I(Ca,L) via cGMP-mediated cAMP-dependent PKA signalling. IP3-dependent Ca2+ signalling may enhance local SR Ca2+ release required to activate Ca2+-dependent eNOS/NOi production from subsarcolemmal caveolae sites.
...
PMID:Phenylephrine acts via IP3-dependent intracellular NO release to stimulate L-type Ca2+ current in cat atrial myocytes. 1594 66

We present here evidence for the enhancement of an inositol 1,4,5-trisphosphate (IP3) mediated calcium signaling pathway in myotubes from dystrophin-deficient cell lines (SolC1(-)) as compared to a cell line from the same origin but transfected with mini-dystrophin (SolD(+)). With confocal microscopy, we demonstrated that calcium rise, induced by the perifusion of a solution containing a high potassium concentration, was higher in SolC1(-) than in SolD(+) myotubes. The analysis of amplitude and kinetics of the calcium increase in SolC1(-) and in SolD(+) myotubes during the exposure with SR Ca2+ channel inhibitors (ryanodine and 2-APB) suggested the presence of two mechanisms of SR calcium release: (1) a fast SR calcium release that depended on ryanodine receptors and (2) a slow SR calcium release mediated by IP3 receptors. Detection analyses of mRNAs (reverse transcriptase [RT]-PCR) and proteins (Western blot and immunolocalization) demonstrated the presence of the three known isoforms of IP3 receptors in both SolC1(-) and SolD(+) myotubes. Furthermore, analysis of the kinetics of the rise in calcium revealed that the slow IP3-dependent release may be increased in the SolC1(-) as compared to the SolD(+), suggesting an inhibitory effect of mini-dystrophin in this signaling pathway. Upon incubation with pertussis toxin (PTX), an inhibitory effect similar to that of the IP3R inhibitor (2-APB) was observed on K+-evoked calcium release. This result suggests the involvement of a Gi protein upstream of the IP3 pathway in these stimulation conditions. A hypothetical model is depicted in which both Gi protein and IP3 production could be involved in K+-evoked calcium release as well as a possible interaction with mini-dystrophin. Our findings demonstrate the existence of a potential relationship between mini-dystrophin and SR calcium release as well as a regulatory role of mini-dystrophin on intracellular signaling.
...
PMID:Mini-dystrophin expression down-regulates overactivation of G protein-mediated IP3 signaling pathway in dystrophin-deficient muscle cells. 1644 5

Sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) are responsible for many physiological functions, including angiogenesis, neuronal survival, and immunity. However, little is known about their effects in modulating the stimulus-secretion coupling in bovine chromaffin cells. The result of PCR showed that at least two receptors (S1P(3) and LPA(1)) were expressed in bovine chromaffin cells. The elevation of [Ca(2+)](i) by S1P was fast and sustaining; but the elevation by LPA was slow and transient. The EC(50) for S1P and LPA in elevating the [Ca(2+)](i) were 0.55+/-0.01 and 0.54+/-0.40microM, respectively. This elevation could be totally blocked by thapsigargin, 2-APB, and U73122. Pertussis toxin pretreatment inhibited about half of the elevation in [Ca(2+)](i) suggesting the involvement of G(i) and other G-proteins. Repetitive [Ca(2+)](i) elevations elicited by S1P, but not LPA, were inhibited by ryanodine. S1P was more effective than LPA in triggering exocytosis as measured by the changes in membrane capacitance. The whole-cell Ca(2+) current was inhibited by both lysophospholipids but Na(+) current was inhibited by S1P only. These results suggest the differential effects of LPA and S1P in releasing Ca(2+) from the intracellular Ca(2+) stores and modulating the stimulus-secretion coupling in bovine chromaffin cells.
...
PMID:Lysophospholipids elevate [Ca2+]i and trigger exocytosis in bovine chromaffin cells. 1661 68

UTP causes interleukin (IL)-6 production via mRNA expression through P2Y(2)/P2Y(4) receptors in human HaCaT keratinocytes. In the present study, we analyzed the mechanism of UTP-induced IL-6 production in these cells. UTP, an agonist of P2Y(2)/P2Y(4) receptors, induced phosphorylation of extracellular signal-regulated kinase (ERK) in a concentration- and time-dependent manner. PD98059, a MEK (mitogen-activated protein kinase kinase) inhibitor, and BAPTA-AM [O,O'-bis(2-aminophenyl)ethyleneglycol-N,N,N',N'-tetraacetic acid, tetraacetoxymethyl ester], an intracellular Ca(2+) chelator, reduced UTP-induced ERK phosphorylation and IL-6 mRNA expression. 2-APB [(2-aminoethoxy)diphenylborane], an inositol 1,4,5-trisphosphate (IP(3))-receptor antagonist, inhibited UTP-induced IL-6 mRNA expression; and the action of A23187, a Ca(2+) ionophore, resembled the action of UTP. In contrast, protein kinase C (PKC) downregulation and pertussis toxin did not affect UTP-induced IL-6 mRNA expression, suggesting that PKC and G(i) are not involved in the UTP-induced IL-6 production. However, AG1478, an epidermal growth factor (EGF)-receptor inhibitor, partially decreased UTP-induced ERK phosphorylation and IL-6 expression. These results suggest that UTP-induced IL-6 production is in part mediated via phosphorylation of ERK through G(q/11)/IP(3)/[Ca(2+)](i) and transactivation of the EGF receptor.
...
PMID:Contribution of extracellular signal-regulated kinase to UTP-induced interleukin-6 biosynthesis in HaCaT keratinocytes. 1713 Jun 74

Lysophosphatidylserine (LPS) can be generated following phosphatidylserine-specific phospholipase A2 activation. The effects of LPS on cellular activities and the identities of its target molecules, however, have not been fully elucidated. In this study, we observed that LPS stimulated intracellular calcium increased in mouse bone marrow-derived mast cells (BMMC), and rat C6 glioma and human HCT116 colon cancer cells and compared the LPS-induced Ca2+ increases with the response by lysophosphatidic acid (LPA), a structurally related bioactive lysolipid. In order to test involvement of signaling molecules in the LPS-induced Ca2+ signaling, we used pertussis toxin (PTX), U73122, and 2-APB, which are specific inhibitors for G proteins, phospholipase C (PLC), and IP3 receptors, respectively. The increases due to LPS and LPA were inhibited by PTX, U-73122 and 2-APB, suggesting that both lipids stimulate calcium signaling via G proteins (Gi/o types), PLC activation, and subsequent IP3 production, although the sensitivity to pharmacological inhibitors varied from complete inhibition to partial inhibition depending on cell type and lysolipid. Furthermore, we observed that Ki16425 completely inhibited an LPS-induced Ca2+ response in three cell types, but that the effect of VPC32183 varied from complete inhibition in BMMC and C6 glioma cells to partial inhibition in HCT116 cells. Therefore, we conclude that LPS increases [Ca2+]i through Ki16425/VPC32183-sensitive G protein-coupled receptors (GPCR), G protein, PLC, and IP3 in mouse BMMC, rat C6, and human HCT116 cells.
...
PMID:Lysophosphatidylserine induces calcium signaling through Ki16425/VPC32183-sensitive GPCR in bone marrow-derived mast cells and in C6 glioma and colon cancer cells. 1840 43

1 2 3 Next >>