Vatariri uye zvigadziko zvavo muPharmacology

Vatengesi uye zvigaro zvavo

Vatariri vekirasi yakafara yePransmemrane mapuratidziro emapuranga emasero ematishini uye anotamba chinzvimbo chakakosha mukudzora chikamu cheganho Aya mapuroteni emamapteni anoita sevachengeti vemasuwo ekutengesa manyoro ekutonga nharaunda yemukati nekuona kuti zvakakosha zvekushandisa, metmones anopinda muchitokisi, nepo madhiragi ane mishonga, kazhinji anopesana nehasha yavo gradient. Muchirevo chePharmacology, "vatakuri vezvinodhaka" vanowanzoreva mapuroteni iya anoshandisa nzira dzakatarwa kuti vatamire vamiriri vezvipingamupinyi zvebhaibheri. Mhuri mbiri huru dzinotonga maitiro aya: ATP - kusunga kaseti (ABC) Superfamily uye iyo Solut Carrier (SLC) SLC) SLC) STUC) SUBLEFAMILY.

ABC Transgers: ATP - Driven Drivakeevers

VaABC Vatariri Vokutanga Vanotakura Vanotakura Vanotakura Simba kubva kuATP Hydrolysis kuti vafambe kusiyanisa kwakasiyana-siyana, zvakadai, uye zvinodhaka-mumhepo mbozs membranes, kunyangwe kurwisa cellularranes. Halmark yeaya maatakuri ndeyekuti avo vakachengetedzwa zvakanyanya nyukireya Simba ravo - Basa Revanhu Rekusakosha harisi kungochengetedza cellular homeostasis uye kutora chikamu mu metabolic detoxification asiwo kune zvinopa kune zvinodhaka kuramba zvinodhaka. Semuenzaniso, nekushingairira kweComotherpeutic vamiriri vekunze, vanodzikisa musangano wemishonga zvinodhaka, nekudaro vachidzikisira mashandiro ekuratidzira uye anotungamira kuwanda kuramba (MDR).

SLC Vatariri veStter: Yakagadziriswa uye Sekondari Inoshanda Systems

Mukupesana neABC vatambi, nhengo dzeSolute Carrier (SLC) SUBLEFILY HONOGONA KUTI VANODA KUTI ATP Hydrolysis. Panzvimbo iyoyo, SLC vatariri vanoshanda zvakanyanya seechikadzi vanoshanda kana kufambisa vatakuri. Ivo vanoshandisa preexisting preexisting electrochemical gradients-vanowanzogadzirwa neEon pumps-yekutyaira vanokwira kana kusunungurwa vakaita seGlucose, Amino Acids, neurotransmitters, uye akasiyana organic ions. Mazhinji madhiragi ayo ari hydrophilic kana kuratidzira akaderera pasombrane premeability ivhu pane idzi vatakuri veCelluly kupinda uye inotevera basa. Nekuti vanofambiswa neIon Gradients kwete ATP

Zvinodhaka efflux zvakasiyana-siyana: inoshanda hunyanzvi

Muchirongwa chakawandisa chekutakura zvinodhaka, dzimwe vatambi vane hunyanzvi hwekushandisa zvinodhaka, vamwe vachifambisa zvinodhaka zvinodhaka. EFLLOX vatambi, kunyanya kubva kumhuri yeABC, shandisa ATP Hydrolysis kusvika kushingairira kubvisa makomendi kubva pamasero. Iri basa rakakosha kuti rigare kudzikamisa pamatisiki emisungo uye yekudzivirira nhengo dzinotyisa. Vanokutyaira, vanowanzoitika mukati memhuri yeSLC, kuendesa zvinodhaka nemamolekyubhi nemamorekuru, achiverenga mabhanhire avo uye anogonesa zviito zvavo zvavakatarwa pharmacological pamasaiti. Pamwe chete, chiitiko chakarongeka cheEfflux uye vanokwira vatakuri vanosarudza iyo plasma yekushambadzira, kugovera, uye ma profiles emazhinji ekurapa makomputa, nekukasira kupesvedzera.

Vatakuri Key uye Zvidimbu zvavo

MDR1 (P - Glycopoletein, ABCB1)

Semumwe weanonyanya kudzidza ABC vatariri veBC, MDR1 (inowanzozivikanwa seP - Nekushingairira kupomba zvinodhaka uye xenobiotic kunze kwemasero, p - GP inogumira mishonga yemugodhi uye inovimbisa kukurumidza kubviswa kubva kune yepakati system system. Clinically, iyo Overexpression yeP - muTumor multrutor yekupokana, dambudziko rinoda kuti ishandiswe zvimwe zviitiko zvekurapa kana kuunganidzira kweMemosensitizers ayo anotadzisa basa rayo. P - kugona kwaGP kutakura yakarongeka yehurongwa hwakasarudzika-kubva kuAnticancer makomputa kusvika kumisheni-anoratidza basa rayo rinokosha mune dzimba dzekudzivirira uye phamacotherapy.

BSEP (Bile Salt Export Pump, ABCB11)

BSEP Chimwe Chiropa - Chairo chairo ABC anokosha kuti akanyatsokosha kune chakanyorwa chakakodzera cheBile Acids kubva kuHepatocytes muBile Canaliculi. Kuita uku kwakakosha kuti uya wekugaya uye kusihwa kwemafuta ezvekudya uye kuchengetedza bile acid homeostasis. Kuvhiringidza kweBSEP basa-kungave kuburikidza ne genetic kuzvitumbuka kana zvinodhaka - inheting inhibition-inogona kukonzera cholestasis, mamiriro ezvinhu anoratidzwa nehurongwa hwekutadza kuyerera. Zvirwere zvechiropa zvechiropa zvinogona kufambira mberi kusvika pakubata kwakanyanya, kugadzira iyo tarisiro inonetsa yezvibodzwa zvinogona kuongorora zvinodhaka zvechiremba uye nekuvandudzwa kwevairatidziro kurapa mamiriro ezvisikwa.

Bcrp (mazamu cancer kuramba mapuroteni, ABCG2)

BcrP imwe ATP - Inotsamira EFFLUX Yekutakura inotaurwa zvakanyanya mumatisiki senge placenta, chiropa, mudumbu, uye ropa-reropa. Muchirevo chezvinodhaka, bcrp inokanganisa hurongwa hwezvirongwa zvevamiriri vekurapa, kusanganisira chomotherapeusicics uye antivirals, nekuvamhora kubva pamasero. Yayo strategic yekumanikidza mumatombo ematehwe anobatsira kuchengetedza fetus uye uropi kubva kuXenobiotic. Genetic dzakasiyana

Mate1 / Mate2 - K (Multidrug uye Toxin Extrusion Mapuroteni)

Vatakuri ava chikamu cheSLC Superfamily uye vanonyanya kuratidzwa muRenal uye Hepatic tishu. Mate1 naMate2 - K shanda pamwe chete neBasolaterally iri mubatanidzwa weCoxic Cation (yakadai se Oct2 muitsvo) kuti ifambe nedanho rezvakanaka zvinobhadharwa nemabhadhoni. Nekuwedzera kweCation Substrates muUrine kana bile, mapuroteni aya anobatsira kuchengetedza zvinodhaka clearance uye kuderedza systemic yehurongwa. Kuvimbika kwavo kwekuvimbika kwakakosha kuti kudzivirira kuunganidzwa kwezvinodhaka, izvo zvinogona kutungamira kune zviitiko zvakashata zvinosanganisira nephrerotortousity.

OATP1B1 (organic anon kutakura polypeptide 1b1, SLCO1B1)

Yakatonyanya kuratidzwa paSinusoidal membrane yeHepatocytes, oatp1b1 ndiyo kiyi yekukwira yekutakura mhirizhonga yemishonga yakasiyana-siyana yemishonga yemishonga yemishonga, inosanganisira statins, mishonga inorwisa mabhakitiriya, uye anticandcer vamiririri. Iyi yekutakura inotakurawo basa rekupindirana mukukwira kweiyo endochuus makomputa akadai saBilirubin, Steroid conjugates, uye mahormone evaHermones. Variants muSLCO1B1 Gene inogona kukanganisa zvakanyanya zvinodhaka pharmacokinetics, semuenzaniso, nekuchinja marongero ekujekesa uye kuwedzera njodzi ye myopathy. Nekuda kweizvozvo, oatp1b1 inzvimbo yepakati inotarisa muPharmacogenomics uye yakasarudzika mushonga.

Oat1 (Organic Anion Transport 1, SLC22A6)

Oat1 inonyanya kuratidzwa pane basoisteral membrane yerenal proximal tubule masero uye ine mutoro wekukwira kweiyo yakafara huwandu hwesangano rezvinyorwa. Aya mavara anosanganisira kwete chete endojesuus metabolites-akadai seyrate uye cyclic quilotides-asiwo exogenious makomputa, kwete - zvinodhaka (mishonga inoshandisa (NSAIDS), uye nemamiriro ekunze. Kusiyana muOat1 basa kana kutaura kunogona kukanganisa zvinodhaka pharmacokinetics uye kupa zvinodhaka - yakanyengerwa nePefleroticxity. Basa rekutakura repakati mukutsvenesa kujekesa kunoita kuti ive yakakosha yekufanidza uye kugadzirisa zvinodhaka zvinodhaka muitsvo.

Pfupiso uye Clinical Zvinoreva

Pamwe chete, aya maatakuri orchestrate a akaomarara network yekunyudza, kugovera, metabolism, uye kushamisika (admE) maitiro akakosha kuPermacotherapy. Chiitiko chavo chakasanganiswa chisingapukunyuki zvekuita zvekurapa uye kuurayiwa kwezvinodhaka asiwo underpins zvakakosha profiti maitiro-kubva kune bile kugadzirwa uye zvinovaka muviri kune detoxication uye njere kutaurirana. Mukukura kwezvinodhaka, kunzwisisa hunhu hwekushanda uye genetic kusiyana kweaya vatariri vanokosha. Inobatsira mukufanotaura zvinodhaka - kutaurirana kwezvinodhaka, kuratidzira kurapa kwemipimo, uye kudzikamisa mhedzisiro yakaipa. Vanotsvagurudza uye varembi vanoramba vachishanda kuti vasike nzira dzakarongeka dzekutakura matanho, vachiramba kukunda matambudziko akadai seyeltidrug kurwisa uye zvinodhaka - kukuvadzwa kweropa kana itsvo kukuvara.

Keywords: ATP - Kusunga Cassette (ABC), SLC Transporder, MDCK: COCE Kuseka, kuseka SLC yekutakura