Imikhiqizo

Imiphumela yezokuhlanza emsebenzini we-P-glycoprotein atpase: umehluko ekuphazamisekeni kwemisebenzi encike ku-basal ne-verapamil.

I-P-glycoprotein (P-gp), i-plasma membrane glycoprotein ehlotshaniswa ne-phenotype yokumelana nezidakamizwa eziningi, inesibopho sokuphuma okuncike ku-ATP kwemithi ehlukahlukene ye-amphiphilic.Sisebenzisa ama-membrane vesicles alungiselelwe kusuka kumugqa weseli ongazweli kwezidakamizwa eziningi DC-3F/ADX, sifunde ukuphazamiseka kwe-basal (okungukuthi lapho kungekho sidakamizwa) kanye nemisebenzi ye-AP-gp encike kuverapamil eyenziwa yizihlanzi ezahlukahlukene, ekungaxubheni, kanye nase-solubilizing, ukugxila.I-solubilization ye-membrane eqhubekayo ngokugxila kokuhlanza okukhulayo kwaqashwa ngokuhlakazeka kokukhanya nokuhlolwa kwe-centrifugation.Ngokugxilisa okokuhlanza okungancibilikisiwe, zonke izinto zokuhlanza ezihloliwe ngaphandle kwe-DOC zenze ukuvinjelwa kancane komsebenzi we-P-gp ATPase, obungahlotshaniswa nenani lezihlanzi ezihloliwe ezihlukahlukene ezifakwe kulwelwesi.Ukuhlaziywa kokuvula i-P-gp eyenziwe yi-verapamil kuveza ukuthi umsebenzi we-P-gp ATPase ulungiswa ngendlela ehlukile yizihlanzi ezahlukahlukene ekugxiliseni okungancibiliki.Ngakho-ke, ukusebenzisana okuqondile phakathi kwe-P-gp nezihlanzi maningi amathuba okuthi kwenzeke kunokuba kuphazamiseke ulwelwesi lomhlaba wonke.Ngemva kokuhlanganiswa kwezinto zokuhlanza ezihloliwe ezihlukahlukene, umsebenzi we-basal we-P-gp ATPase wacishe wavalwa ngokuphelele, ngaphandle kokuba khona kwe-CHAPS ekwazile ukulondoloza lo msebenzi ezingeni eliqhathaniswa nalelo elikalwa kulwelwesi lwendabuko.Nokho, ukusebenza kwe-P-gp ATPase okwenziwe i-verapamil kuye kwalahleka ngesikhathi sokuhlanganiswa kwe-P-gp yi-CHAPS, kodwa kwalulama ngemva kokuhlanjululwa kwe-CHAPS ngaphansi kokugxilisa kwayo okubalulekile kwe-micellar.Lokhu kubuka kubonisa ukusebenzisana okuthile phakathi kwama-molecule e-P-gp kanye ne-CHAPS ngaphakathi kwama-micelles axubile.Sekukonke, idatha yethu efakazela ukusebenzisana okuthile kwe-P-gp/izinto zokuhlanza ziyahambisana nendawo yezindawo zokuthutha izidakamizwa ezizindeni ze-P-gp transmembrane.