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)

In systemic vasculitis, interactions between antineutrophil cytoplasm autoantibodies (ANCAs) and neutrophils initiate endothelial and vascular injury. ANCAs directed against either myeloperoxidase (MPO) or proteinase 3 (PR3) can activate cytokine-primed neutrophils by binding cell surface-expressed MPO or PR3, with the concurrent engagement of Fcgamma receptors (FcgammaR). Because roles for phospholipase D (PLD) and phosphatidylinositol 3 kinase (PI3K) have been demonstrated in FcgammaR activation of neutrophils, this study investigated the hypothesis that ANCA stimulation of neutrophils involved a similar engagement of FcgammaR and activation of PLD and PI3K. Pretreatment of tumor necrosis factor (TNF) alpha-primed neutrophils with antibodies against FcgammaRII and FcgammaRIII inhibited MPO-ANCA and PR3-ANCA induced superoxide generation, confirming that FcgammaR ligation is involved in ANCA-mediated neutrophil activation. However, although stimulation of TNF-alpha-primed neutrophils by conventional FcgammaR ligation, either using antibody-mediated cross-linking of FcgammaR or aggregated IgG, induced PLD activation, ANCA stimulation did not. Moreover, although ANCA-induced neutrophil activation results in significant PI3K activation-as assessed by phosphatidylinositol 3,4,5-triphosphate generation-conventional FcgammaR ligation, but not ANCA, activates the p85/p110 PI3K subtype. Inhibition of ANCA-induced superoxide generation with pertussis toxin suggests that ANCAs activate the p101/p110gamma PI3K isoform. In addition, the kinetics of activation of protein kinase B differs between conventional FcgammaR ligation and ANCA stimulation of neutrophils. These results demonstrate that though ligation of FcgammaRIIa and FcgammaRIIIb may be necessary, it is likely that ANCAs require other membrane cofactors for neutrophil activation.
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PMID:Antineutrophil cytoplasm autoantibodies from patients with systemic vasculitis activate neutrophils through distinct signaling cascades: comparison with conventional Fcgamma receptor ligation. 1152 Jul 94

Microglial cells, the macrophages of the brain, express low, yet detectable levels of cannabinoid CB(1) receptors, which are known to modulate cell migration. To determine if cannabinoid CB(1) receptors expressed by microglial cells modulate their migration, we assessed whether arachidonylcyclopropylamide (ACPA, an agonist shown to selectively activate CB(1) receptors) affects the migration of BV-2 cells, a mouse microglial cell line. We found that ACPA induced a dose-dependent increase in BV-2 cell migration (EC(50)=2.2 nM). This ACPA response was blocked by pertussis toxin pretreatment, suggesting the involvement of G(i/o) protein-coupled receptors. However, the cannabinoid CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamidehydrochloride (SR141716A) did not prevent ACPA-induced BV-2 cell migration. Two antagonists of cannabinoid CB(2) receptors N-(1,S)-endo-1,3,3-trimethyl bicyclo(2,2,1)heptan-2-yl)-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528) and cannabinol, as well as two antagonists of the newly identified "abnormal-cannabidiol-sensitive" (abn-CBD) receptors (O-1918 and cannabidiol) prevented this response. Our results suggest that cannabinoid CB(2) receptors and abn-CBD receptors, rather than cannabinoid CB(1) receptors, regulate microglial cell migration, and that ACPA is a broad cannabinoid receptor agonist.
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PMID:Arachidonylcyclopropylamide increases microglial cell migration through cannabinoid CB2 and abnormal-cannabidiol-sensitive receptors. 1292 61

This study aimed to investigate the function of the cannabinoid receptor in the neuromuscular junction of the frog (Rana pipiens). Miniature end-plate potentials were recorded using the intracellular electrode recording technique in the cutaneous pectoris muscle in the presence of the cannabinoid agonists WIN55212-2 (WIN; R-(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)]-pyrolol[1,2,3de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone) and arachidonylcyclopropylamide [ACPA; N-(2-cyclopropyl)-5Z,8Z,11Z,147-eicosatetraenamide] and the cannabinoid antagonists 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-4-morpholinyl-1H-pyrazole-3-carboxamide (AM281) and 6-iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1H-indol-3-yl](4-methoxyphenyl)methanone (AM630). Adding WIN to the external medium decreased the frequency and amplitude of the miniature end-plate potentials (MEPPs); the WIN EC50 value was 5.8+/-1.0 microM. Application of ACPA, a selective agonist of cannabinoid receptor CB1, also decreased the frequency of the MEPPs; the ACPA EC50 value was 115.5+/-6.5 nM. The CB2 antagonist AM630 did not inhibit the effects of WIN, indicating that its action is not mediated through the CB2 receptor. However, the CB1 antagonist AM281 inhibited the effects of WIN and ACPA, suggesting that their actions are mediated through the CB1 receptor. Pretreatment with the pertussis toxin inhibited the effects of WIN and ACPA, suggesting that their effects are mediated through Gi/o protein activation. The N-type Ca2+ channel blocker omega-conotoxin GVIA (omega-CgTX) diminished the frequency of the MEPPs, with an omega-CgTX EC50 value of 2.5+/-0.40 microM. Blocking the N-type Ca2+ channels with 5 microM omega-CgTX before addition of ACPA to the bath had no additional inhibitory effect on the MEPPs, whereas in the presence of 1 microM omega-CgTX, ACPA had an additional inhibition effect. These results suggest that cannabinoids modulate transmitter release in the end-plate of the frog neuromuscular junction by activating CB1 cannabinoid receptors in the nerve ending.
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PMID:Effects of cannabinoids on synaptic transmission in the frog neuromuscular junction. 1726 83

Indian red scorpion (Mesobuthus tamulus; MBT) envenomation produces various cardio-respiratory abnormalities including cardiac dysrhythmias. The underlying cell signaling pathways for the cardiac dysrhythmias produced by MBT venom are not known. The present study was therefore conducted to delineate the second messenger signaling pathways involved in MBT venom-induced atrial rhythm changes. The effects of venom and various antagonists were examined on spontaneously beating rat right atrial preparations in vitro. The MBT-venom produced an increase (35%), a decrease (45%) and again an increase (50%) in rate at 0.03, 0.3 and 3.0 microg/ml of venom, respectively. On the other hand, force of contraction exhibited a concentration-dependent rise (up to 40%) at all concentrations of venom. Pretreatment with atropine (0.3 microM) blocked the decrease in atrial rate at 0.3 microg/ml concentration of venom while no such blockade was seen in force of contraction. Submaximal concentration of ACh (0.1 nM) decreased the atrial rate by 25%. In the presence of MBT venom (0.3 microg/ml), ACh-induced fall in atrial rate was enhanced. The venom-induced fall in atrial rate and augmentation of ACh response were blocked by pertussis toxin (PTx; a Gi-inhibitor) or methylene blue (a G-cyclase inhibitor). The results indicate that the decrease in atrial rate produced by venom is mediated muscarinic by receptors via Gi-guanylyl cyclase mediated cell signaling pathways.
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PMID:Bradycardia induced by Mesobuthus tamulus scorpion venom involves muscarinic receptor-G-protein-coupled cell signaling pathways. 1851 31

The effect of cannabinoids on caffeine contractures was investigated in slow and fast skeletal muscle fibers using isometric tension recording. In slow muscle fibers, WIN 55,212-2 (10 and 5 microM) caused a decrease in tension. These doses reduced maximum tension to 67.43 +/- 8.07% (P = 0.02, n = 5) and 79.4 +/- 14.11% (P = 0.007, n = 5) compared to control, respectively. Tension-time integral was reduced to 58.37 +/- 7.17% and 75.10 +/- 3.60% (P = 0.002, n = 5), respectively. Using the CB(1) cannabinoid receptor agonist ACPA (1 microM) reduced the maximum tension of caffeine contractures by 68.70 +/- 11.63% (P = 0.01, n = 5); tension-time integral was reduced by 66.82 +/- 6.89% (P = 0.02, n = 5) compared to controls. When the CB(1) receptor antagonist AM281 was coapplied with ACPA, it reversed the effect of ACPA on caffeine-evoked tension. In slow and fast muscle fibers incubated with the pertussis toxin, ACPA had no effect on tension evoked by caffeine. In fast muscle fibers, ACPA (1 microM) also decreased tension; the maximum tension was reduced by 56.48 +/- 3.4% (P = 0.001, n = 4), and tension-time integral was reduced by 57.81 +/- 2.6% (P = 0.006, n = 4). This ACPA effect was not statistically significant with respect to the reduction in tension in slow muscle fibers. Moreover, we detected the presence of mRNA for the cannabinoid CB(1) receptor on fast and slow skeletal muscle fibers, which was significantly higher in fast compared to slow muscle fiber expression. In conclusion, our results suggest that in the slow and fast muscle fibers of the frog cannabinoids diminish caffeine-evoked tension through a receptor-mediated mechanism.
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PMID:Effects of cannabinoids on caffeine contractures in slow and fast skeletal muscle fibers of the frog. 1950 35