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)

The present work was undertaken to study the metabolic response of C6 glioma cells to physiologically relevant doses of delta9-tetrahydrocannabinol (THC), the major active component of marijuana. At those concentrations (i.e. nanomolar range), THC produced a dose-dependent increase in the rates of glucose oxidation to CO2 and glucose incorporation into phospholipids and glycogen. The THC-induced stimulation of glucose utilization was (i) dose-dependent up to 100 nM THC, (ii) mimicked by the synthetic cannabinoid HU-210, and (iii) prevented by pertussis toxin and the CB1 receptor antagonist SR141716A. In contrast to THC, forskolin markedly depressed CO2 production, phospholipid synthesis and glycogen synthesis from glucose. The forskolin-induced inhibition of glucose utilization was (i) mimicked by dibutyryl-cAMP, and (ii) prevented by THC, HU-210 and H-7, an inhibitor of the cAMP-dependent protein kinase. Likewise, THC was able to antagonize in part the forskolin-induced elevation of intracellular cAMP concentration, and this antagonistic effect was prevented by SR141716A. However, THC per se did not affect basal cAMP concentration. Results thus indicate that physiologically relevant doses of THC stimulate glucose metabolism in C6 glioma cells through a cannabinoid receptor-mediated process. Although cannabinoid receptors may be coupled to inhibition of adenylyl cyclase in C6 glioma cells, this does not seem to be the mechanism involved in the THC-induced stimulation of glucose metabolism.
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PMID:Delta9-tetrahydrocannabinol stimulates glucose utilization in C6 glioma cells. 936 16

The present study of newborn pig cerebral circulation investigated the role of pertussis toxin (PTX)-sensitive GTP binding proteins in the permissive action of prostacyclin in specific dilator responses. Pial arterioles of anesthetized piglets were observed through closed cranial windows. The piglets were treated topically with PTX and intravenously with indomethacin. The effects of hypercapnia (10% CO2 ventilation) and topical 5,6-epoxyeicosatrienoic acid (5,6-EET) on pial arteriolar diameter were noted before and after the intervention. Samples of the artificial cerebrospinal fluid (aCSF) were collected from beneath the cranial windows for determination of the cAMP concentration. After administration of PTX, indomethacin still abolished pial arteriolar dilation to both hypercapnia and 5, 6-EET and also inhibited the cAMP elevation caused by hypercapnia. The addition of phorbol 12-myristate 13-acetate (PMA), but not iloprost, restored the increase in cAMP and vascular responses to hypercapnia and 5,6-EET. Therefore, in the newborn pig cerebral microvasculature, PTX appears to inhibit a G protein involved in the permissive action of prostacyclin. However, the protein kinase C (PKC) activator PMA appears to act downstream from the block, and, therefore, the permissive action of PMA is not affected by PTX. We suggest that the prostacyclin IP receptor may be coupled to phospholipase C via a PTX-sensitive G protein that normally permits vasodilation to specific stimuli via activation of a PKC, resulting in phosphorylation of a component of the adenylyl cyclase pathway.
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PMID:PTX-sensitive G proteins and permissive action of prostacyclin in newborn pig cerebral circulation. 968 22

The effects of cannabinoids on metabolic pathways and signal transduction systems were studied in primary cultures of rat astrocytes. Delta9-Tetrahydrocannabinol (THC), the major active component of marijuana, increased the rate of glucose oxidation to CO2 as well as the rate of glucose incorporation into phospholipids and glycogen. These effects of THC were mimicked by the synthetic cannabinoid HU-210, and prevented by forskolin, pertussis toxin, and the CB1 receptor antagonist SR 141716. THC did not affect basal cAMP levels but partially antagonized the forskolin-induced elevation of intracellular cAMP concentration. THC stimulated p42/p44 mitogen-activated protein kinase (MAPK) activity, Raf-1 phosphorylation, and Raf-1 translocation to the particulate cell fraction. In addition, the MAPK inhibitor PD 098095 and the phosphoinositide 3-kinase inhibitors wortmannin and LY 294002 were able to antagonize the THC-induced stimulation of glucose oxidation to CO2, phospholipid synthesis and glycogen synthesis. The possible involvement of sphingomyelin breakdown in the metabolic effects of THC was studied subsequently. THC produced a rapid stimulation of sphingomyelin hydrolysis that was concomitant to an elevation of intracellular ceramide levels. This effect was prevented by SR 141716. Moreover, the cell-permeable ceramide analog D-erythro-N-octanoylsphingosine, as well as exogenous sphingomyelinase, were able in turn to stimulate MAPK activity, to increase the amount of Raf-1 bound to the particulate cell fraction, and to stimulate glucose metabolism. The latter effect was prevented by PD 098059 and was not additive to that exerted by THC. Results thus indicate that THC produces a cannabinoid receptor-mediated stimulation of astrocyte metabolism that seems to rely on sphingomyelin hydrolysis and MAPK stimulation.
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PMID:Involvement of sphingomyelin hydrolysis and the mitogen-activated protein kinase cascade in the Delta9-tetrahydrocannabinol-induced stimulation of glucose metabolism in primary astrocytes. 980 18

Cell-free lung lavage fluid (LLF) from healthy normal rats killed phase I (wild-type, virulent) Bordetella pertussis at 37 degrees C in vitro. B. parapertussis was also killed by the LLF, but phase IV (avirulent mutant) B. pertussis and some other common bacterial species, including B. bronchiseptica, were not. Transmission electron microscopy of thin sections of the phase I B. pertussis showed extensive structural damage and cell lysis. None of the other mammalian species tested had LLF with bactericidal activity against B. pertussis as high as that of the rat. Rats killed with halothane yielded LLF with higher bactericidal activity than when CO2 was used. Ultracentrifugation of LLF at 55,000 g gave a surfactant (pellet) fraction that had c. 95% of the bactericidal activity and which was biochemically distinct from the 5% of activity in the supernate fraction. Phospholipids and fatty acids appeared to be involved in LLF bactericidal activity, but not complement or lysozyme. Arachidonic acid was the most active of the fatty acids tested. Artificial surfactant, as used in premature infants, had no bactericidal effect on B. pertussis.
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PMID:Bactericidal activity of rat lung lavage fluid against Bordetella pertussis. 1040 14

The effects of lysophosphatidic acid (LPA) on ovum transport in mouse oviducts were studied. When excised oviducts were incubated at 37 degrees C under 5% CO2 in humidified air for 24 hours, addition of LPA at 10 microM to the medium significantly accelerated the rate of ovum transport, and 1 microM LPA slightly increased the ovum transport rate. These increases were not inhibited by 10 microM indomethacin, a cyclooxygense inhibitor, but were suppressed by 260 ng/ml of pertussis toxin or 10 microM verapamil, a voltage-sensitive calcium channel blocker. These data suggested that LPA stimulates mouse ovum transport by contracting oviductual smooth muscle via a voltage-sensitive calcium channel mediated by a pertussis toxin-sensitive G-protein-linked receptor.
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PMID:Effect of lysophosphatidic acid on the ovum transport in mouse oviducts. 1046 49

Adenosine is a defensive metabolite that is critical to anoxic neuronal survival in the freshwater turtle. Channel arrest of the N-methyl-d-aspartate receptor (NMDAR) is a hallmark of the turtle's remarkable anoxia tolerance and adenosine A1 receptor (A1R)-mediated depression of normoxic NMDAR activity is well documented. However, experiments examining the role of A1Rs in regulating NMDAR activity during anoxia have yielded inconsistent results. The aim of this study was to examine the role of A1Rs in the normoxic and anoxic regulation of turtle brain NMDAR activity. Whole-cell NMDAR currents were recorded for up to 2 h from turtle cortical pyramidal neurons exposed to pharmacological A1R or Gi protein modulation during normoxia (95% O(2)/5% CO2) and anoxia (95% N2/5% CO2). NMDAR currents were unchanged during normoxia and decreased 51+/-4% following anoxic exposure. Normoxic agonism of A1Rs with adenosine or N6-cyclopentyladenosine (CPA) decreased NMDAR currents 57+/-11% and 59+/-6%, respectively. The A1R antagonist 8-cyclopentyl-1,3-dimethylxanthine (DPCPX) had no effect on normoxic NMDAR currents and prevented the adenosine and CPA-mediated decreases in NMDAR activity. DPCPX partially reduced the anoxic decrease at 20 but not 40 min of treatment. The Gi protein inhibitor pertussis toxin (PTX) prevented both the CPA and anoxia-mediated decreases in NMDAR currents and calcium chelation or blockade of mitochondrial ATP-sensitive K+ channels also prevented the CPA-mediated decreases. Our results suggest that the long-term anoxic decrease in NMDAR activity is activated by a PTX-sensitive mechanism that is independent of A1R activity.
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PMID:Adenosine A1 receptor activation mediates NMDA receptor activity in a pertussis toxin-sensitive manner during normoxia but not anoxia in turtle cortical neurons. 1845 5


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