[Cysteinyl leukotrienes and their receptors].
Cysteinyl leukotrienes (LTC4, LTD4, LTE4) have a proinflamation effect, such as contraction of blood vessels smooth muscle and the respiratory tract, chemotaxis of proinflammatory cells increased endothelium cells permeability and mucus secretion. They are lipid mediators playing an important part in the pathophysiology of bronchial asthma, allergic rhinitis, atopic dermatitis, urticaria, cardiovascular system disorders and tumors. They act through at least four receptors from the rhodopsin gene family, lying in the area of GPCR genes superfamily--CYSLTR1, CYSLTR2, GPR17 and receptor for LTE4 (CYSLT(E)R). Their location, apart from small exceptions, is differentiated and typical for tissues. The highest CYSLTR1 expression was stated in the spleen, peripheral blood leucocytes, interstitial lung macrophage and smooth muscle cells. CYSLTR2 shows highest expression in the hearth, adrenal glands, placenta, spleen and peripheral blood leucocytes, and somewhat smaller in the brain. Biochemical and pharmacological study and the analysis of sequences have shown that all three types of receptors belong to the group of 7-transmembrane receptors--GPCR. The CYSLTR1 excitation power is distributed: LTD4>LTC4>LTF4, and CYSLTR2 LTC4=LTD4>LTE4. Cysteinyl leukotrienes receptors are coupled with the G(q/11) proteins and signal path leading to phosphatidylinositol hydrolysis (PI) and mobilization of intracellular calcium. These receptors are in vivo coupled with the PTX-sensitive G(q/11) protein or both G proteins. CYSLTR1 increases the metabolism of PI and intracellular calcium, activates MAPK kinases, induces differentiation and proliferation of cells, chemotaxis, actin reorganization, release of inflammation mediators and regulation of hematopoietic stem cells. CYSLTR2 also increases the concentration of intracellular calcium, stimulates the release of IL-8 and increases expression of early genes. It is connected to thrombosis, vessel damage, inflammation process and cell death. The existence of new, nuclear, localization of CYSLTR and coexistence with other membrane receptors is postulated. It is probable that they can crate homo- or heterodimers. This indicates the existence of new, previously not know actions of, cysteinyl leukotrienes and their receptors.
Wódz-Naskiewicz
Karolina
K
Zakład Immunopatologii, Katedra Alergologii, Immunologii i Dermatologii, Uniwersytet Medyczny w Łodzi, Łódź, Poland. kwodz@csk.umed.lodz.pl
Pawliczak
Rafał
R
D000818:Animals; D001249:Asthma / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000503:physiopathology; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D003876:Dermatitis, Atopic / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009130:Muscle, Smooth / Q000378:metabolism; D009369:Neoplasms / Q000503:physiopathology; D018077:Receptors, Leukotriene / Q000378:metabolism*; D012220:Rhinitis / Q000503:physiopathology; D015398:Signal Transduction / Q000502:physiology; D013154:Spleen / Q000378:metabolism
D008565:Membrane Proteins; D018077:Receptors, Leukotriene; C083169:leukotriene D4 receptor