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

Purinoceptor agonists produced potassium currents with the order of potency: ATP > adenosine = ADP = AMP > beta,gamma-methylene ATP, while a small response or no response was induced by 2-methylthio ATP, UTP, or alpha,beta-methylene ATP. The response induced by beta,gamma-methylene ATP was completely inhibited in the presence of alpha,beta-methylene ATP, suggesting that the relevant receptor for these agonists was a P3 purinoceptor. ATP induced currents with a latency of 24 s and the currents were not induced in defolliculated oocytes. The currents were not affected by either the Gi/o-protein inhibitor, pertussis toxin (PTX), or the selective cAMP-dependent protein kinase inhibitor, H-89, or the phospholipase C (PLC) inhibitor, neomycin, or the phospholipase A2 (PLA2) inhibitor, 4-bromophenacyl bromide. The currents were enhanced by the selective protein kinase C (PKC) inhibitor, GF109203X, but otherwise, they were reduced by the potent PKC activator, 12-O-tetradecanoylphorbol-13-acetate. The results of the present study suggest that a P3 purinoceptor in the follicle cell layer of oocytes is involved in activation of potassium channels and that the evoked currents are regulated by PLC/PLA2-independent PKC activation.
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PMID:ATP produces potassium currents via P3 purinoceptor in the follicle cell layer of Xenopus oocytes. 965 60

Adenosine triphosphate (ATP) is a signaling molecule for brain cells including astrocytes. In these cells, it has been shown that ATP stimulates myelin basic protein (MBP) kinase activity which is believed to represent the Erk family of MAP kinases. Indeed, we show that ATP activates simultaneously MBP kinase activity and phosphotyrosine incorporation in p42 Erk2 and p44 Erk1. Maximal effect of ATP is obtained at 50 microM after 5 min and disappears after 60 min. Effect of ATP is mimicked by 2-methylthio-ATP whereas alpha beta-methyleneadenosine 5' triphosphate (AMP-CPP) and adenosine do not promote any effect. Uridine triphosphate (UTP) activates also p42 and p44 MAP kinases. These observations indicate that p42-p44 MAP kinases activation can be obtained through P2v and P2u receptors. Purinergic stimulation of Erk is insensitive to pertussis toxin which inactivates heterotrimeric Gi protein. It is not inhibited by a PLA2 inhibitor (4 bromophenacyl bromide [B phi B]) and the PI3 kinase inhibitor, wortmannin. In contrast, purinergic stimulation of Erk is partially inhibited by the PKC inhibitor. GF109203X, at 5 microM and suppressed when extracellular calcium is complexed by ethylene glycol-bis(2-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA).
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PMID:Ca2+ dependent purinergic regulation of p42 and p44 MAP kinases in astroglial cultured cells. 975 13

We have isolated, from canine pancreatic juice, two 14-kDa proteins with secretin-releasing activity that had N-terminal sequence homology with canine pancreatic phospholipase A2 (PLA2). In this study we have obtained evidence that secretin-releasing activity is an intrinsic property of pancreatic PLA2. Porcine pancreatic PLA2 from Sigma or Boehringer Mannheim was fractionated into several peaks by reverse phase high performance liquid chromatography. They were tested for stimulation of secretin release from murine neuroendocrine intestinal tumor cell line STC-1 and secretin cells enriched mucosal cell preparations isolated from rat upper small intestine. Each enzyme preparation was found to contain several components of secretin-releasing activity. Each bioactive fraction was purified to homogeneity by rechromatography and then subjected to mass spectral analysis and assays of PLA2 and secretin-releasing activities. It was found that the fraction with highest enzymatic activity also had the highest secretin-releasing activity and the same Mr as porcine pancreatic PLA2. Moreover, it also had the same N-terminal amino acid sequence (up to 30 residues determined) as that of porcine pancreatic PLA2, suggesting that it was identical to the enzyme. Purified porcine pancreatic PLA2 also stimulated secretin release concentration-dependently from both STC-1 cells and a mucosal cell preparation enriched in secretin-containing endocrine cells isolated from rat duodenum. Abolishment of the enzymatic activity by pretreatment with bromophenacyl bromide did not affect its secretin-releasing activity. The stimulatory effect of purified pancreatic PLA2 on secretin secretion from STC-1 cells was inhibited by an L-type Ca2+ channel blocker, by down-regulation of protein kinase C or by pretreatment of the cell with pertussis toxin. It is concluded that porcine pancreatic PLA2 possesses an intrinsic secretin-releasing activity that was independent of its enzymatic activity. This action is pertussis toxin-sensitive and is in part dependent on Ca2+ influx through the L-type channel and activation of protein kinase C.
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PMID:Porcine pancreatic phospholipase A2 stimulates secretin release from secretin-producing cells. 1019 48

We investigated the Ca(2+) signaling pathways of the response to angiotensin II in pleural mesothelial cells and the role of these Ca(2+) signaling pathways in mesothelial cell proliferation. Rat pleural mesothelial cells were maintained in vitro, and the Ca(2+) movement to angiotensin II was evaluated using the fluorescent Ca(2+) indicator fura 2. Furthermore, proliferation of mesothelial cells was assessed using a spectrophotometric 3-(4, 5-dimethylthazol-2-yl)-2,5-diphenyl-2H-tetrasodium bromide (MTT) assay. Angiotensin II (1 pM-100 microM) induced in mesothelial cells a biphasic elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)) that consisted of a transient initial component, followed by a sustained component. Neither removal of extracellular Ca(2+) nor inhibition of Ca(2+) influx by 1 microM nifedipine affected the angiotensin II-induced initial transient elevation of [Ca(2+)](i) in mesothelial cells. Nifedipine did not block angiotensin II-induced sustained elevation of [Ca(2+)](i). Angiotensin II (1 pM-100 microM) had a proliferative effect on mesothelial cells in a dose-dependent manner. Angiotensin II type 1 (AT(1)) receptor antagonist ([Sar(1), Ile(8)]angiotensin II) inhibited both angiotensin II-induced elevation of [Ca(2+)](i) and proliferation of mesothelial cells. Pertussis toxin did not affect angiotensin II-induced responses. These results suggest that angiotensin II-induced responses to mesothelial cells are extremely dependent on the angiotensin AT(1) receptor coupled with pertussis toxin-insensitive G protein.
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PMID:Angiotensin II type 1 receptor-mediated increase in cytosolic Ca(2+) and proliferation in mesothelial cells. 1065 43

An investigation of the possible interactions between combinations of vaccines and pyridostigmine bromide (PB) has been undertaken in the guinea pig. This study is part of a research programme funded by the UK Government to determine any effects of the pretreatment regimes given to UK Forces during the Persian Gulf conflict of 1990-1991. The study was designed to simulate PB administration and to model multiple vaccination protocols that were experienced by UK Forces, modelling a "worst case" situation in which all ten vaccines and PB were administered within a short period of time. Seven of the vaccines were health and hygiene (H+H) vaccines given to protect against endemic diseases and two vaccines to protect against the biological warfare agents anthrax and plague. In addition, pertussis vaccine was administered as an adjuvant to reduce the time to achieve immunity against anthrax. Four groups of eight animals were treated with 1/20th, 1/10th or 1/5th human doses of vaccines or vehicles, respectively. The PB or saline was delivered by implanted 28 day mini-osmotic pumps to achieve a mean red blood cell acetylcholinesterase (AChE) inhibition of around 30%. Body weight, temperature, immunological response, biochemical indices and spontaneous activity were monitored for 72 days. Although immunological responses to bacterial vaccines were observed, there were no remarkable findings in the parameters measured other than minor changes in body weight (4.9% decrease at the 1/5th human dose of vaccines) and temperature increases in response to vaccination. Animals in all groups remained generally healthy and active without visible adverse signs throughout the study. Reproduced with the permission of Her Majesty's Stationery Office. Published by John Wiley & Sons, Ltd.
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PMID:Biological consequences of multiple vaccine and pyridostigmine pretreatment in the guinea pig. 1118 Feb 81

Dopamine (DA) is a physiological regulator of PRL secretion, exerting tonic inhibitory control. DA activates an inward rectifier K(+) (IRK) channel in rat lactotropes, causing membrane hyperpolarization and inhibition of Ca(2+)-dependent action potentials. Both the activation of this effector K(+) channel and the inhibition of PRL release are mediated by D(2)-type receptor activation and pertussis toxin- sensitive G proteins. To study the molecular basis of this physiologically relevant channel, a homology-based PCR approach was employed to identify members of the IRK channel family expressed in the anterior pituitary gland. Nondegenerate primers corresponding to regions specific for IRK channels known to be G protein activated (GIRKs; gene subfamily Kir 3.0) were synthesized and used in the PCR with reverse transcribed female rat anterior pituitary messenger RNA as the template. PCR products of predicted sizes for Kir 3.1, 3.2, and 3.4 were consistently observed by ethidium bromide staining after 16 amplification cycles. The identities of the products were confirmed by subcloning and sequencing. Expression of each of these gene products in anterior pituitary was confirmed by Northern blot analysis. Functional analysis of the GIRK proteins was performed in the heterologous expression system, Xenopus laevis oocytes. Macroscopic K(+) currents were examined in oocytes injected with different combinations of Kir 3.0 complementary RNA (cRNA) and G protein subunit (beta(1)gamma(2)) cRNA. The current-voltage relationships demonstrated strong inward rectification for each individual and pairwise combination of GIRK channel subunits. Oocytes coinjected with any pair of GIRK subunit cRNA exhibited significantly larger inward K(+) currents than oocytes injected with only one GIRK channel subtype. Ligand-dependent activation of only one of the GIRK combinations (GIRK1 and GIRK4) was observed when channel subunits were coexpressed with the D(2) receptor in Xenopus oocytes. Dose-response data fit to a Michaelis-Menten equation gave an apparent K(d) similar to that for DA binding in anterior pituitary tissue. GIRK1 and GIRK4 proteins were coimmunoprecipitated from anterior pituitary lysates, confirming the presence of native GIRK1/GIRK4 oligomers in this tissue. These data indicate that GIRK1 and GIRK4 are excellent candidate subunits for the D(2)-activated, G protein-gated channel in pituitary lactotropes, where they play a critical role in excitation-secretion coupling.
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PMID:Identification of G protein-coupled, inward rectifier potassium channel gene products from the rat anterior pituitary gland. 1141 1

We have previously demonstrated that the release of arachidonic acid (AA) from human chorionic gonadotropin (hCG)-stimulated Leydig cells occurs in a dose- and time-dependent manner. In addition, the amount of AA released was dependent on the hormone-receptor interaction and the concentration of LH-hCG binding sites on the cell surface. The present study was conducted to evaluate the involvement of phospholipase A(2) (PLA(2)) and G proteins in AA release from hormonally stimulated rat Leydig cells, and the possible role of this fatty acid in cAMP production. Cells were first prelabelled with [(14)C]AA to incorporate the fatty acid into cell phospholipids, and then treated in different ways to evaluate AA release. hCG (25 mIU) increased the release of AA to 180+/-12% when compared with AA released from control cells, arbitrarily set as 100%. Mepacrine and parabromophenacyl bromide (pBpB), two PLA(2) inhibitors, decreased the hormone-stimulated AA release to 85+/-9 and 70+/-24% respectively. Conversely, melittin, a PLA(2) stimulator, increased the release of AA up to 200% over control. The inhibitory effect of mepacrine on the release of AA was evident in hCG-treated Leydig cells, but not in the melittin-treated cells. To determine if the release of AA was also mediated through a G protein, cells were first permeabilized and subsequently treated with pertussis toxin or GTPgammaS, a non-hydrolyzable analog of GTP. Results demonstrate that GTPgammaS was able to induce a similar level of the release of AA as hCG. In addition, pertussis toxin completely abolished the stimulatory effect of hCG on the release of AA, indicating that a member of the G(i) family was involved in the hCG-dependent release of AA. Cells treated with PLA(2) inhibitors did not modify cAMP production, but exogenously added AA significantly reduced cAMP production from hCG-treated Leydig cells, in a manner dependent on the concentration of AA and hCG. Results presented here suggest an involvement of PLA(2) and G proteins in the release of AA from hCG-stimulated Leydig cells, and under particular conditions, regulation of cAMP production by this fatty acid in these cells.
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PMID:Arachidonic acid release from rat Leydig cells: the involvement of G protein, phospholipase A2 and regulation of cAMP production. 1178 77

Recently, cannabinoids (CBs) have been shown to possess antitumor properties. Because the psychoactivity of cannabinoid compounds limits their medicinal usage, we undertook the present study to evaluate the in vitro antiproliferative ability of cannabidiol (CBD), a nonpsychoactive cannabinoid compound, on U87 and U373 human glioma cell lines. The addition of CBD to the culture medium led to a dramatic drop of mitochondrial oxidative metabolism [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide test] and viability in glioma cells, in a concentration-dependent manner that was already evident 24 h after CBD exposure, with an apparent IC(50) of 25 microM. The antiproliferative effect of CBD was partially prevented by the CB2 receptor antagonist N-[(1S)-endo-1,3,3-trimethylbicyclo[2,2,1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528; SR2) and alpha-tocopherol. By contrast, the CB1 cannabinoid receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboximide hydrochloride (SR141716; SR1), capsazepine (vanilloid receptor antagonist), the inhibitors of ceramide generation, or pertussis toxin did not counteract CBD effects. We also show, for the first time, that the antiproliferative effect of CBD was correlated to induction of apoptosis, as determined by cytofluorimetric analysis and single-strand DNA staining, which was not reverted by cannabinoid antagonists. Finally, CBD, administered s.c. to nude mice at the dose of 0.5 mg/mouse, significantly inhibited the growth of subcutaneously implanted U87 human glioma cells. In conclusion, the nonpsychoactive CBD was able to produce a significant antitumor activity both in vitro and in vivo, thus suggesting a possible application of CBD as an antineoplastic agent.
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PMID:Antitumor effects of cannabidiol, a nonpsychoactive cannabinoid, on human glioma cell lines. 1461 82

The mechanisms of diethylstilbestrol (1 to 30 microM)-induced relaxation on noradrenaline (30 nM)-raised tone in the rat aorta smooth muscle were studied. Neither the increase of calcium content in the medium (3, 6 and 9 mM) nor Bay K 8644 (3, 10 and 100 nM) reversed diethylstilbestrol relaxation. Tamoxifen (3 microM), the quaternary derivate (tamoxifen ethyl bromide, 3 microM), actinomycin D (30 microM), cycloheximide (100 microM), Rp-cAMPS (30 microM), TPCK (1 microM) and difluoromethylornithine (1 mM) inhibited diethylstilbestrol-induced relaxation. Incubation with 2 microg/ml pertussis toxin, propranolol (1 microM), H-7 (10 microM), 2',3'- and 2',5'-dideoxiadenosine (10 and 30 microM, respectively) and methylene blue (10 microM) did not modify diethylstilbestrol-induced relaxation. Our results showed that presumably an activation of membrane mechanisms, protein kinase A activation, genomic mechanisms and polyamine synthesis might participate in diethylstilbestrol-elicited relaxation in addition to the increase in K(ATP) permeability, as previously described. Actinomycin D produces a synergistic effect, with tamoxifen, difluoromethylornithine and glibenclamide antagonizing the effect of diethylstilbestrol. In the case of the association of actinomycin D and glibenclamide, the antagonism of relaxation is complete. The fact that tamoxifen- and difluoromethylornithine-dependent mechanisms participate in diethylstilbestrol relaxation inhibited by glibenclamide suggests that two transduction pathways are involved in the relaxation. Therefore, K(ATP) channels and genomic mechanisms, both modulated by cyclic AMP (cAMP)-dependent mechanisms, are associated with diethylstilbestrol relaxation.
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PMID:Mechanisms of diethylstilbestrol-induced relaxation in rat aorta smooth muscle. 1474 26

Skeletal muscle differentiation follows an organized sequence of events including commitment, cell cycle withdrawal, and cell fusion to form multinucleated myotubes. The role of adenosine 5'-triphosphate (ATP)-mediated signaling in differentiation of skeletal muscle myoblasts was evaluated in C(2)C(12) cells, a myoblast cell line. Cell differentiation was inhibited by P2X receptor blockers or by degradation of endogenous ATP with apyrase. However, pertussis toxin, known to block only a group of P2Y receptors, did not alter the differentiation process. Cells were heterogeneous in their expression of functional P2X receptors, evaluated by the uptake of fluorescent permeability tracers (Lucifer yellow and ethidium bromide), and by immunofluorescence of P2X(7) receptors. Moreover, xestospongin C, a selective and membrane-permeable inhibitor of IP(3) receptors, inhibited both myotube formation and myogenin expression. Based on these results, we suggest that the known increase in intracellular Ca(2+) concentration required for differentiation is due at least in part to Ca(2+) influx through P2X receptors and Ca(2+) release from intracellular stores. The possible involvement of P2X receptors and other pathways that might set the intracellular Ca(2+) at the level required for myoblast differentiation as well as the possible involvement of gap junction channels in the intercellular transfer of second messengers involved in coordinating myogenesis is proposed.
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PMID:The formation of skeletal muscle myotubes requires functional membrane receptors activated by extracellular ATP. 1557 71


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