Analysis of the Leukotriene D&lt;sub&gt;4&lt;/sub&gt; Receptor in the Granulation Tissue of Allergic Inflammation in Rats

Hirasawa, Noriyasu; Hoshi, Tomonori; Kudoh, Michiko; Mue, Suetsugu; Tsurufuji, Susumu; Watanabe, Miki; Ohuchi, Kazuo

doi:10.1159/000236342

Cited by 2 publications

(2 citation statements)

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“…) and E % , the constituents of the slow-reacting substance of anaphylaxis, are extremely potent and have a large number of physiological effects [1,3]. These effects are generally agreed to be mediated via the interaction of the leukotrienes with specific plasma membrane receptors on the affected cells [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

“…Although no information is available regarding amino acid and nucleotide sequences, the LTD % receptor has been characterized as a G-protein-coupled receptor in several types of inflammatory and non-inflammatory cells [7,10]. This is partly due to the findings that the LTD % receptor interacts physically with a pertussis toxin-sensitive G-protein [6] and that pertussis toxin impairs certain aspects of the signalling capacity of the LTD % receptor in both inflammatory [6,11] and non-inflammatory cells [12].…”

Section: Introductionmentioning

confidence: 99%

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Leukotriene D4-induced mobilization of intracellular Ca2+ in epithelial cells is critically dependent on activation of the small GTP-binding protein Rho

Grönroos

Andersson

Schippert

et al. 1996

Biochemical Journal

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We have previously shown that the leukotriene D4 (LTD4)-induced mobilization of intracellular Ca2+ in epithelial cells is mediated by a G-protein that is distinctly different from the pertussis toxin-sensitive G-protein that regulates the subsequent influx of Ca2+. In the present study, we attempted to gain further knowledge about the mechanisms involved in the LTD4-induced mobilization of intracellular Ca2+ in epithelial cells by investigating the effects of compactin, an inhibitor of the isoprenylation pathway, on this signalling event. In cells preincubated with 10 microM compactin for 48 h, the LTD4-induced mobilization of intracellular Ca2+ was reduced by 75% in comparison with control cells. This reduction was reversed by co-administration of mevalonate (1 mM). The effect of compactin occurred regardless of whether or not Ca2+ was present in the extracellular medium, suggesting that isoprenylation must occur before Ca2+ is released from intracellular stores. In accordance with this, we also found that both the LTD4-induced formation of inositol 1,4,5-trisphosphate and the LTD4-induced phosphorylation of phospholipase C gamma 1 (PLC gamma 1) on tyrosine residues were significantly reduced in compactin-pretreated cells. These results open up the possibility that the activation of PLC gamma 1 is related to a molecule that is sensitive to impaired activity of the isoprenylation pathway, such as a small monomeric G-protein. This idea was supported by the observation that Clostridium botulinum C3 exoenzyme-induced inhibition of Rho proteins abolished the LTD4-induced intracellular mobilization of Ca2+. A regulatory role of Rho proteins in the LTD4-induced activation of PLC gamma 1 is unlikely to be indirectly mediated via an effect on the cytoskeleton, since cytochalasin D had no major effect on the LTD4-induced mobilization of Ca2+. Although the mechanism of interaction remains to be elucidated, the present findings indicate an important role of an isoprenylated protein such as Rho in the LTD4-induced Ca2+ signal.

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