Zoyendera ndi maudindo awo mu pharmacology

Zoyendera ndi maudindo awo

Zoyendera ndi gulu la masinthidwe osinthika omwe amatenga minyewa ya cell yomwe imakhala ndi gawo lofunikira pakuwongolera ma endo nativa (mwachilengedwe (zachilendo) zinthu. Mapuloteni a member a membrane awa amachita monga maofesi oyang'anira ma cell amkati mwa kuwonetsetsa kuti michere yofunikayi, pomwe mahomoni amalowa mu cell, pomwe mahomoni amaloledwa, nthawi zambiri amakhala ndi cholinga chawo. Munthawi yonse ya pharmacology, "zonyamula mankhwala osokoneza bongo" nthawi zambiri amatanthauza matebulo omwe amagwiritsa ntchito njira zapadera zothandizira othandizira kudutsa zotchinga zachilengedwe. Mabanja awiri akuluakulu amalamulira izi: The Atp - kumanga kaseti (ABC) Superfaamu ndi onyamula solumu (slc) superfamamly.

ABC Kuyendetsa: ATP - Kuyendetsa Zipata Zithunzi

Maulendo a ABC ndi oyendetsa ogwirira ntchito omwe amagwira ntchito kuchokera ku ATP Hydrolysis kuti asunthe mitundu yambiri, monga ma cepraner, ngakhale mankhwala osokoneza bongo ambiri. Chizindikiro cha zoyendera izi ndi Nyukinto yosungidwa bwino kwambiri - imangiriza (NBDS) yomwe imamangiriza itp, ndi ma tracembrane angapo omwe amapereka kudzera munjira ina. Mphamvu zawo - Ntchito yodalirana sizovuta osati kusunga ma cell hometostasis komanso kutenga nawo mbali mu metabolic detomiritsation komanso popereka mankhwala osokoneza bongo. Mwachitsanzo.

Makina oyendetsa: ophunzitsidwa ndi sekondale

Mosiyana ndi zonyamula ma abc, mamembala onyamula sonone (slc) nthawi zambiri safuna kuwongolera ATP Hydrolysis. M'malo mwake, ma trans oyendetsa bwino kwambiri ngati achiwiri ogwiritsa ntchito kapena oyendetsa. Amagwiritsa ntchito ma elekitiromical elextrocher, nthawi zambiri amapangidwa ndi ion mapampu - kuyendetsa a ion. Mankhwala ambiri omwe ndi hydrophilic kapena kuwonetsa kutsika pang'ono pang'onopang'ono kumadalira zoyendera izi zama cell polowetsa komanso ntchito yotsatira. Chifukwa amayendetsedwa ndi ion gradents osati ma atp, zonyamula ma slc nthawi zambiri zimapereka njira zotsimikizika kwambiri zowunikira gawo lapansi ndi mayendedwe ake omwe ndi ofunikira.

Mankhwala a mankhwala osokoneza bongo

Munjira yonse yonyamula katundu, zonyamula zina ndizothandiza kwa mankhwala osokoneza bongo, pomwe ena amatsogolera utali wa mankhwala. Zoyendetsa ku banja la ABC, gwiritsani ntchito ATP Hydrolysis kuti muchotse mankhwala kuchokera maselo. Ntchitoyi ndiyofunika kuchepetsa mayamwidwe pamitundu yotchinga komanso yoteteza ziwalo zomveka. Pabwino wonyamula, makamaka mkati mwa banja la SLC, amapereka mankhwala osokoneza bongo komanso mamolekyulu achizindikiro m'maselo, ndikuonetsetsa kuti bioacacalor imachita bwino pamasamba omwe akufuna. Pamodzi, zomwe zikugwirizana ndi zoyendetsedwa za Edlux ndi zoyendetsa zimapangitsa kuti plasma ikhale ya plasma, magawidwe, komanso kuwongolera ma prestery ambiri ochiritsa, potengera mphamvu ndi pomsic.

Zoyendetsa zazikulu ndi maudindo awo

MDR1 (P - Glycoprotein, Abcb1)

Monga imodzi mwamayendedwe omwe a ABC adaphunzitsidwa kwambiri Mwa kupukuta mankhwala ndi ma Xenobiotics kunja kwa maselo, p - GP malire mkaka pamlomo wamankhwala ndikuwonetsetsa kuchotsedwa mofulumira ndi chapakati mantha dongosolo. Zachipatala, kuchuluka kwa p - GP mu zotupa ndi othandizira kwambiri ku kukana zinthu zambiri, vuto lomwe limafunikira kugwiritsa ntchito njira zosachiritsira kapena kupatsirana kwa mankhwalawa. P - Kutha kwa GP kunyamula magawo angapo osagwirizana - kuchokera ku Anticancer othandizira kupita ku maantibayotiki, akuwonetsa mbali yofunika kwambiri mumimba yoteteza ndi pharmacotherapy.

Bsep (fu lamchere lotumiza mchere wotumidwa, Abcb11)

BSEAP ndi chiwindi - Kugulitsa mwachindunji kwa ABC ndikofunikira kuti biri yoyenera ya bile acids kuchokera ku hepatocytes mu bile canalikuli. Njirayi ndiyofunikira kuti chimbudzi chikhale chofunikira komanso mayamwidwe amafuta zakudya komanso kukhalabe a acididid homestasis. Kusokonezeka kwa BSEP Kugwiritsa ntchito ma genetic kapena mankhwala - Kubwezeretsedwanso - kumatha kuchitika ku cholestasis, kumachitika chifukwa cha kuwonongeka kwa bile. Chowonjezera chiwindi chitha kupita patsogolo mpaka hepatotoxicity yolimba, ndikupanga bsep chovuta chowunikira mankhwala a hepatotoxic komanso kukula kwa ochiritsa pochita chorestatic mikhalidwe.

BCRP (khansa ya m'mawere yokana mapuloteni, Abcg2)

BCRP ndi ATP Wina - Kutengera kwa ogwirira ntchito omwe amafotokozedwa kwambiri mu minofu monga placenta, chiwindi, matumbo, ndi chotchinga cha magazi. Munthawi yonse ya mankhwala osokoneza bongo, BCRP imachepetsa kuwonekera kwa othandizira, kuphatikizapo chemotherapetics ndi ma antivirals, powaponda m'maselo. Malingaliro ake mu minyewa yotchinga amathandiza kuteteza mwana wosabadwayo ndi ubongo wochokera ku Xenobiotic. Kusiyana kwa majini kapena kutanthauzira kwa BCRP kumatha kusintha bioaavalobility ndipo yakhala ikuphatikizidwa pakukaniza chemotherapy, ndikupangitsa kukhala chinthu chofunikira kwambiri mankhwala ndi mankhwala a pharmacokinetic.

Mate1 / Mate2 - k (kildrug ndi ma protein otayika)

Zoyenda izi ndi gawo la SLC Superfamamily ndipo limafotokozedwa makamaka mu aimpso komanso hepatic. Mate1 ndi MAte2 - K Ntchito Yolumikizana ndi Badenly adapeza zonyamula makonda (monga Oct2 mu impso) kuti mupange chimbudzi cha mankhwala osokoneza bongo ndi poizoni. Mwa kutayidwa mu mkodzo kapena bile, mapuloteni amenewa amathandizira kusunga mankhwala osokoneza bongo ndikuchepetsa kuwopsa kwadongosolo. Kukhulupirika kwawo ndikofunikira kuti titeteze kudzikundikira kwa mankhwala, komwe kumatha kuchititsa kuti zinthu zizichitika kuphatikiza nephrotoxicity.

Oatp1b1 (organic anion onyamula polypeptide 1b1, slco1b1)

Makamaka nembanemba ya hepatocytes, oatp1b1 ndi njira yofunikira kwambiri yomwe imayambitsa matenda osiyanasiyana, kuphatikizapo ma statins, maanticaotic, ndi othandizira anticancer. Chotsatsa ichi chimagwiranso ntchito yofunika kwambiri pazinthu zam'mapapo monga bilirubin, steroid curjakuta, ndi mahomoni a chithokomiro. Zosiyanasiyana mu SLCCA1B1 zimatha kukhudza kwambiri pharmacokinetics, mwachitsanzo, posintha mafinya a zigawo za ma statins ndikuwonjezera chiopsezo cha mypathy. Zotsatira zake, oatp1b1 ndi gawo lofunikira kwambiri mu pharmacogenogenomics ndi mankhwala.

Oat1 (Organic Anion Stear 1, SLC22A6)

Oat1 imafotokozedwa makamaka pa barrane ya aimpso ma cell chumbale chubulo ndipo imayambitsa kukweza kwa majeremita okhwima kuchokera m'magazi. Mitundu iyi imasandulika ma metabolis okhaokha, monga urate ndi cyclic nucleotides, komanso mitundu yosiyanasiyana ngati mankhwala osokoneza bongo (NSAIDS), ndi poids. Kusintha kwa oat1 ntchito kapena mawu kumatha kusokoneza mankhwala am'mapiri a mankhwala ndikuthandizira ku mankhwala - nephrotoxicity. Gawo lalikulu la chiletso mu vomerezedwe chimapangitsa kuti ikhale yofunika kwambiri yolosera komanso kugwiritsa ntchito mankhwala osokoneza bongo azomwe zimachitika mu impso.

Chidule ndi zovuta zamankhwala

Pamodzi, zonyamula izi zimayambitsa kuyamwa kovuta, kugawa, kagayidwe kagayidwe kake, ndi mawu (adme) omwe ndi ofunikira ku pharmacyherapy. Kuchita kwawo kophatikizika kumangokhudza kuchiritsa kwa mankhwala komanso kupweteketsa mankhwala osokoneza bongo komanso zotheka kuphatikizika ndi mafomu a bile komanso zolimbitsa thupi. Pokula kwa mankhwala, kumvetsetsa mawonekedwe ndi ma genetics ndi kusiyanasiyana kwa ma genetic kwa oyendetsa kumeneku ndikofunikira. Zimathandizira kulosera za mankhwala - Zogwirizana ndi Mankhwala, kuphatikizira Mankhwala Othandizira, ndikusokoneza zovuta zake. Ofufuzawo ndi asidi amagwira ntchito mosalekeza kuti athe kugwiritsa ntchito njira zomwe zidachitika poyendetsa, akufuna kuthana ndi zovuta monga kukana monga kukana chiwopsezo kapena kuvulala kwa impso.

Mawu osakira: ATP - Cassette (ABC), ABC Kuyendetsa, Mdmby, OATP1B1 Kafukufuku, hek293 mock, mock slureter