
sisteenail leukotrian risapttar 1

sisteenail leucotrian risapttar 1, csltr 1 ennum ariyappedunnu, ithu sisteenail leucotrians (elty)-nte oru resepteraanu (leukotrienes#cysteinyl leucotrians kaanuka). eee sisteenail ell. tii. esine (csl. tii. sii. 4, ell. tii. dii. 4, ell. tii. iii. 4) bandhippikkunnathiloode, manushyarile vividha allergy, hypersensitivity prathikaranangalkkum mattu mrugangalile prathikaranangalude maathrkakalkkum madhyasthatha vahikkaan csl. tii. aarr. 1 sahayikkunnu.
jeane.
xq13-xq21 enna sthaanathu x chromosomilake manushya jeane maappil, exon 3 ll sthithicheyyunna muzhuvan ooppan reeding frame 337 amino aasidukal adangiya oru proteinulla kodukalum ulkkollunnu. sisaltru 1" jeane promoter mekhala athinte transcription staartt saittinte 665 muthal 30 bipi vare mukalilaanu.
aavishkaaram.
shwaasakoshathile minusamarnna peshikal, shwaasakosha macrophageukal, monocytukal, eosynophils, basophils, neutrophils, platelettukal, tii cellukal, bii lymphocyteukal, pluripottant hematopoitic stem cellukal (sidi34 +), maast cellukal, pancreas, cherukudal, prostettu, naasika mucosayude intersteeshyal cellukal, shwaasanaalathile minusamarnna peshi cellukal, bronchial fibroblastukal, vascular endothelial cellukal ennivayil sisaltru 1 mrna prakadippikkunnu.
pravartthanam.
kosha tharatthe aashrayich athinte sisalt ligaandukalumaayi bandhippikkukayum bandhippikkukayum cheyyumbol athinte cuppled jii proteente jikyu alfa subunit koodaathe/allengil gaa subunit sajeevamaakkukayum cheiyunna oru jii protein-cuppled resepteraanu sisaltru 1. eee jii proteinukaliloodeyum avayude upavibhaagangaliloodeyum pravartthikkunna ligand-boundu sisalttar 1 kosha pravarthanatthilekku nayikkunna niravadhi pathakal sajeevamaakkunnu (vishadaamshangalkku jii. kyu. alfa <aii. dii. 1>, gaa <aii. dii. 1> enniva kaanuka); uthejippikkunna sysulter 1-nte shakthiyude kramam ell. tii. dii. 4> ell. tii. sii 4> ell. tii. iii 4 aanu, ell. tii. iii 4-nuu vivoyile sysulter 1-ll pravartthikkunna kooduthal pravarthanangalkku mathiyaya sakthiyilla.
mrugangalude modalukalilum manushyarilum ell. tii. sii. 4,/allengil ell tii. dii. dii. 4 enniva vazhi sisal. tii. aarr 1 sajeevamaakkunnath shwaasanaala broncoconstriction histaamain polulla broncoconstriction ejantukalodulla hyper responsivalum; vardhicha vascular permiability, edema, eosynophillukaludeyum neutrofillukaludeyum ozhukk, sugamamaya peshi vyaapanam, kolajan nikshepam, vividha tissue saittukalile fibrosis; goblettu koshangal, goblettu sell metaapleshya, shwaasakosha sisttathinte stharangalile epithelial sell hypertrophy enniva vazhi musine sravam. mrugangalude maathrkayum manushya koshangalum (preclinical padanangal) mastishka parikk (aaghaatham, ischemia, jaladosham enniva), multiple sclerosis, oottoo immyoon encephalomyelitis, alsheimer rogam, paarkkinsans rogam ennivayude modalukalil samrakshana/nashtaparihara phalangal ullathayi sisalttar 1 athiraalikale aaropikkunnu. mrugangalude maathrkakalil raktha-mastishka thadassam kuraykkunnathumaayi (athaayath.iii. rakthathil layikkunna gadakangalilekku mastishka kaappilarikalude praveshanakshamatha vardhippikkuka) athupole mastishka koshangalilekkulla rakthathinaayulla leukositeukalude chalanathe prolsaahippikkuka; eee phalangal apasmaram pidipedunnathinte vikaasavum aavruthiyum vardhippikkukayum echuaivi-1 polulla leukosite parathunna vairasukalude mastishka koshangalilekku praveshanam vardhippikkukayum cheyyum.
moothrasanchi, neuroblastoma, mattu mastishka arbudangal, prostettu arbudam, stanarbudam, vankudal arbudam (crc) ennivayude traansishanal sell carsinomayil sisaltrar 1-nte vardhicha aavishkaaram nireekshikkappettundu; theerchayaayum, sisaltrar 1 tumour expression sthanaarbudathileyum crc rogikalileyum mosham athijeevana roganirnayavumaayi bandhappettirikkunnu, koodaathe sisaltru 1-nte drugg inhibittarukal yathaakramam crc koshangaludeyum tumourukaludeyum inn vivo, inn vivo (animal model) valarchaye thadayunnu. sii. aarr. sii koshangalude vyaapanavum athijeevanavum vardhippikkunna paathakale niyantrikkaanulla kazhivu kaaranam sii. aarr. siyile sisal. tii. aarr. 1-nte cancer anukoola phalangal prathyakshappedunnu. 
mattu sislt resepterukalil sisteenail leukotrian risapttar 2 (i.iii. sisaltru 2), gpr99 (ooksogloottarett risapttar ennum chilappol sisaltru 3 ennum vilikkunnu). uthejippikkunna sisaltru2-nte shakthiyude kramam eltidi4 = eltisi4> elte4 aanu, elte4-nuu vivoyile sisaltru2-ll pravartthikkunna dhaaraalam pravartthanangal nadatthaan mathiyaya sakthiyilla. gpr99 sisalttukalkk, prathyekichu elte4-nuu oru pradhana resepteraayi kaanapedunnu. gpr99-yude kurravulla elikal ulla gpr99-vahikkunna koshangale uthejippikkunnathil sisalttukal elte4> eltisi4> eltidi4-nte aapekshika sakthikal kaanikkunnu, ithu elte4-lake charmmatthile vascular permiability prathikaranangalude alavu-ashrita nashtam kaanikkunnu, pakshe eltisi4 allengil eltidi4-lake allah. ithum mattu daattayum soochippikkunnathu elte4-nte inn vivo pravarthanangalkku gpr99 oru pradhana resepteraanennu, pakshe elte4 allengil eltisi4-lake allah.
yuraasil nucleotide/sisteenail leukotrian risapttar ennum vilikkappedunna gpr 17 resepterine thudakkathil eltisi 4, eltidi 4, yuraasil nucleotideukal ennivayude resepteraayi nirvachichirunnu. ennirunnaalum, vividha laborattarikalil ninnulla sameepakaala padanangalkku eee phalangal sthireekarikkaan kazhinjilla; gpr 17 vahikkunna koshangal eee sisalttukalumaayo nucleodideukalumaayo prathikarikkunnillenn avar kandethi, ennaal sisalttar 1, gpr 17 resepterukal enniva prakadippikkunna koshangal eltisi 4 bindingle ganyamaaya kuravu prakadippichathaayum gpr 17 illaatha elikal ige-induced passive cutaneous anaphylaxicinode hyper-response cheiyunnuvennum kandethi. athinaal eee model sisttangalil kuranjathu sisaltru 1 neey gpr 17 thadayunnathaayi kaanapedunnu. eee padanangalil ninnu thikachum vyathyasthamayi, neural tissuekalile padanangalude eakaagrathayil oligodendrosite projenittar koshangal gpr 17 prakadippikkukayum eee resepteriloode eltisi 4, eltidi 4, chila purinukal ennivayodu prathikarikkukayum cheiyunnuvennu kandethunnu (gpr17#function kaanuka).
purinergic risapttar, p2y12, nerittu sisalttukalumaayi bandhippikkukayo prathikarikkukayo cheyyaathe, sisalt 1 sajeevamaakkunnathinte anantharafalamaayi sajeevamaanenn thonnunnu risapttar depletion allengil pharmacological reethikal vazhi p2y12 sajeevamaakkunnath thadayunnathu sisalttarinte pala sysulter 1-ashrita pravarthanangaleyum vividha kosha tharangalile inn vitroyilum allergy rogathinte mruga maathrkayilum thadayunnu.
ligandukal.
pradhana sisalttukal athaayath.neutrophils, eosynophils, basophils, monocytukal, macrophageukal, maast cellukal, dendritik cellukal, bii-lymphocyteukal thudangiya veekkam, allergy, mattu rogaprathirodha prathikaranangal enniva niyanthrikkunnathil earppettirikkunna koshangal pradhaanamaayum alox 5 enna 5-lipoxijanes ensime nirmmikkunna arachidonic aasidinte metabolittukalaanu eltisi 4, eltidi 4, elte 4 enniva. alox 5 arachidonic aasidine 5,6-epoxide mungamiyaaya ell. tii. eiii 4 lake metabolis cheiyunnu, ithu pinneedu ell. tii. sii 4 synthase pravartthikkukayum athu γ-glutamile-sisttainil-glycine tripeptide (i.iii. gloottathayon) intermediattinte kaarban 6 lake maarunnathiloode eltisi 4 synthase roopappedunnu. eltisi4 pinneedu emrp1 transporteriloode (abc1) uthbhava koshangalil ninnu purathukadakkukayum kosha uparithalathil gadippichirikkunna gamma-glutamile transferase, depeptidase peptidays ensimeukal enniva vazhi athivegam eltidi4 lake pinneedu elte4 lake parivartthanam cheyyukayum cheiyunnu.
jeane polymorphism.
sisaltru 1" enna coding mekhalayile jeane polymorphism (nucleotide taimin "sisaltru 1" jeeninte 97-aamm sthaanathu cytosine maattisthaapikkunnu) 927t/c (sisaltru 1 jeeninte 97-aamm sthaanathu cytosine maattisthaapikkunnu), attoppiyude theevrathayekkurichu pravachikkunnathayi theliyikkappettittund (i.iii. chila allergy hypersensitivity prathikaranangal vikasippikkunnathinulla oru pravanatha), ennaal aasthmayumaayi bandhappettathalla, yunaittad kingdatthile southaamptan pradeshathu ninnulla rogabadhitharaaya sahodara-jody kudumbangalile 341 kokkeshyan janasamkhyayil. eee attoppi theevratha sthree sahodarangalil ettavum prakadamaayirunnu, ennaal eee polymorphysatthinte sambhavangal valare kuravaanu, koodaathe 927t/c jeeninteyum athinte uthppanna proteinteyum pravartthanam ithuvare anjjaathamaanu.
thekkan atlaantik samudrathile cheria vidoora dveepaaya tristaan daa kunhayile (266 sthiravum janithakamaayi otappettathumaaya nivaasikal) janasamkhyayil attoppi, aasthma ennivayude uyarnna vyaapanam anubavikkunnu. sisaltru1 jeane" uthppanna vakabhedam, 300 gram/seey (i.iii. amino assid glycine sisaltre1 proteente 300 sthaanathu sereene maattisthaapikkunnu), eee janasamkhyayil ithu attoppiyumaayi ganyamaayi bandhappettirikkunnave theliyikkappettittund. sisaltru1 300ezz vakabhedam eltidi4, eltisi4 ennivayodulla vardhicha samvedanakshamatha prakadippichu, eee hypersensitivity attoppiyumayulla bandhathinu adivarayidunnuvennu soochippikkunnu.
klinikkal praadhaanyam.
sisalttukalodu prathikarikkunna mattu resepterukal undengilum, manushyarile sisalttukalodulla pala paatholajikkal prathikaranangalkkum madhyasthatha vahikkunnathil sisalttar 1 nirnaayakamaanennu thonnunnu. montelukaast, safirlukaast, praanlukkast enniva sisaltre1-nuu selective risapttar athiraalikalaanu, pakshe sisaltre2-nuu ethiralla. eee marunnukal upayogathilundu koodaathe/allengil allergy-induced aasthma, rinitis, aspirin-execreated respiratory disease, vyayaamam, thanutha vaayu induced aasthma (vyayaamam-induced broncoconstriction kaanuka), adenotonsillaar hypertrophy moolamulla balyakaala sleep apnia (aquared noonn-inflammatory myopathy#diet, trama induced mayoppathi) enniva polulla allergy, allergy ithara rogangalkkulla roganirodhanavum vittumaaraatha chikilsakalum aayi phalapradamaanennu kaanikkunnu. ennirunnaalum, eee marunnukalodulla prathikaranangal valare vyathyaasappettirikkunnu, marunnukal valare uyarnna nirakkil mosham prathikaranangal kaanikkunnu, koodaathe eee ejantukalumaayulla chikilsaykku sesham rogalakshanangalil mattamonnum report cheyyaatha rogikalude aidi 1. sisaltru 2, gpr99, allengil mattu resepterukal ennivayude sisalttukalodulla prathikaranangal eee rogangalkk kaaranamaakumenn thonnunnu.

