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)

Endothelin-1 (ET-1) and parathyroid hormone (PTH) increase calcium transients in rodent osteoblastic cells. To investigate the role of phospholipase C (PLC) in these hormone-stimulated calcium signals, the effects of U-73122 (1-[6-[[17 beta-3-methoxyestra-1,3,5(10)- trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione), a reported PLC inhibitor, and its inactive analog, U-73343 (1-[6[[17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]- 1H-pyrrolidine-2,5-dione), were determined. Intracellular calcium transients were measured in UMR-106 cells with the fluorescent indicator fluo-3. In normal calcium containing medium, prior exposure (3 min) to U-73122 inhibited ET-1 and PTH stimulated calcium transients in a dose-dependent (0.2-10 microM) manner with an IC50 of 1.5-1.8 microM. A concentration of 6-8 microM was required for complete inhibition of responses to 100 nM ET-1 or PTH. U-73343 elicited no effects over this concentration range. In cells in which external calcium was reduced to less than 1 microM by the addition of EGTA, ET-1 signals were completely inhibited by 4-6 microM U-73122 and the IC50 was 0.8 microM. In the low external calcium medium, the PTH response was abolished by 2 microM U-73122 (IC50 = 0.5 microM). U-73122, 8 microM, significantly (P < 0.01) inhibited the effect of ET-1 on inositol trisphosphate production at 3 min whereas U-73343 did not. Pertussis toxin (100 ng/ml) likewise significantly inhibited the effect of ET-1 on phosphoinositol turnover as well as on intracellular calcium concentration. In conclusion, the results support the hypothesis that PLC plays a role in the calcium transients elicited by ET-1 and PTH, and that ET-1 transmits its signal in part via a pertussis toxin sensitive G-protein coupled receptor. Furthermore they suggest that U-73122 is useful for investigating PLC-mediated process in osteoblastic cells.
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PMID:U-73122, a phospholipase C antagonist, inhibits effects of endothelin-1 and parathyroid hormone on signal transduction in UMR-106 osteoblastic cells. 780 18

Addition of thrombin to isolated [3H]inositol-labelled rat right atria stimulated the release of 3H-labelled inositol phosphates. The thrombin response was smaller than the response to noradrenaline and generated a different spectrum of inositol phosphates. Unlike the inositol phosphate response to noradrenaline, the thrombin response was inhibited by pertussis toxin treatment and by the phospholipase C inhibitor U-73122 (1-(6-((17 beta-3- methoxyestra-1,3,5(10)-trien-17-yl)amino)amino)hexyl)-1H- pyrrole-2, 5-dione). The data indicate that the thrombin stimulation involves different G-proteins and phospholipase C isoforms from those which couple alpha 1-adrenoceptors in the myocardium.
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PMID:The inositol phosphate response to thrombin in rat right atria differs from the response to noradrenaline. 856 74

We conducted studies to investigate the nature and underlying mechanisms of the vascular effects of rutaecarpine (Rut), an alkaloid isolated from the Chinese herbal drug Evodia rutaecarpa. By using largely the effects on phenylephrine (PE)-induced contraction in the isolated rat aorta as the experimental index and by comparison with several known vascular muscle relaxants such as acetylcholine (ACh), histamine, and A23187, Rut relaxed PE-precontracted aorta in concentration-(10(-7)-10(-4) M) and endothelium-dependent manners. Studies with appropriate antagonists indicated that this was coupled to nitric oxide (NO) and guanylyl cyclase. Extracellular Ca2+ removal and treatment with the intracellular Ca2+ antagonist, 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), suggested that influx of extracellular Ca2+ was the major factor contributing to the action of Rut. Pertussis toxin suppressed the relaxation potency of histamine but had no effects on the actions of Rut. NaF, the G proteins activator, attenuated the actions of ACh, but only minimally affected Na-NP, A23187, and Rut. 1-[6-{[17 beta-3-methoxyestra-1,2,3(10)-trien-17-yl]amino} hexyl]-1H-pyrrole-2,5-dione (U73122), the phospholipase C inhibitor, again suppressed the actions of ACh but had few effects on A23187 and Rut. Taken together, these results suggest that these vasorelaxants had different cellular mechanisms and that neither pertussis toxin-sensitive Gi protein, other G proteins, nor phospholipase C activation was involved in the cellular response to rutaecarpine.
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PMID:Studies of the cellular mechanisms underlying the vasorelaxant effects of rutaecarpine, a bioactive component extracted from an herbal drug. 915 59

We present evidence that stimulation of the human beta-3 adrenergic receptor (AR), expressed in Chinese hamster ovary/K1 cells, specifically activates the mitogen-activated protein kinases extracellular signal-regulated kinase (ERK)1 and 2, but not JNK or p38. The extent and kinetics of the ERK stimulation by the beta-3 AR are identical with those of the endogenic insulin receptor. However, insulin augments cellular proliferation, whereas beta-3 AR agonists inhibit proliferation due to the production of cyclic AMP. The pharmacological profile of the ERK activation by the beta-3 AR differs significantly from its activation of adenylyl cyclase. The order of potency and intrinsic activities of both natural ligands, norepinephrine and epinephrine, is inversed between both signaling pathways. In addition, BRL 37344 and propranolol, ligands that act as agonists in the stimulation of cyclase, act as antagonists for ERK activation. The activation of ERK1/2 is sensitive to pertussis toxin, suggesting that the beta-3 AR, in addition to its interaction with Gs, can couple to Gi/o. Furthermore, the activation of ERK by the beta-3 AR is sensitive to PD98059, wortmannin, and LY294002, indicating a crucial role for mitogen-activated protein kinase kinase and phosphatidylinositol-3 kinase (PI3K), respectively. A beta-3 AR-mediated stimulation of PI3K is confirmed by the observation that the selective agonist CGP 12177A specifically activates protein kinase B. As was observed for the activation of ERK, the activation of protein kinase B is inhibited by preincubation with pertussis toxin and PI3K inhibitors, suggesting that both are a consequence of a Gi/o-mediated activation of PI3K.
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PMID:Stimulation of the extracellular signal-regulated kinase 1/2 pathway by human beta-3 adrenergic receptor: new pharmacological profile and mechanism of activation. 992 16

The diverse physiological functions of histamine are mediated through distinct histamine receptors. Mast cells are major producers of histamine, yet effects of histamine on mast cells are currently unclear. The present study shows that histamine induces chemotaxis of mouse mast cells, without affecting mast cell degranulation. Mast cell chemotaxis toward histamine could be blocked by the dual H3/H4 receptor antagonist thioperamide, but not by H1 or H2 receptor antagonists. This chemotactic response is mediated by the H4 receptor, because chemotaxis toward histamine was absent in mast cells derived from H4 receptor-deficient mice but was detected in H3 receptor-deficient mast cells. In addition, Northern blot analysis showed the expression of H4 but not H3 receptors on mast cells. Activation of H4 receptors by histamine resulted in calcium mobilization from intracellular calcium stores. Both G alpha i/o proteins and phospholipase C (PLC) are involved in histamine-induced calcium mobilization and chemotaxis in mast cells, because these responses were completely inhibited by pertussis toxin and PLC inhibitor 1-[6-[[17 beta-3-methoxyestra-1,3,5 (10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U73122). In summary, histamine was shown to mediate signaling and chemotaxis of mast cells via the H4 receptor. This mechanism might be responsible for mast cell accumulation in allergic tissues.
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PMID:Histamine H4 receptor mediates chemotaxis and calcium mobilization of mast cells. 1262 56