API-Ibiyobyabwenge Peptide Linaclotide: Ikinini cyo kugabanya amara no guhumurizwa

Linaclotide ni peptide ya cyclicale igizwe na aside amine 14, eshatu muri zo ni sisitemu ikora imiyoboro ya disulfide.Linaclotide ifitanye isano na peptide ya endogenous peptide guanylin na uroguanylin, ni ligande karemano ya guanylate cyclase C (GC-C).Ikirangantego cya GC-C kigaragarira hejuru yumubiri wa selile epithelial selile, aho igenga imyunyu ngugu nigenda ryimbere.Linaclotide ihuza reseptor ya GC-C ifitanye isano ryinshi kandi yihariye, ikanayikora mu kongera urwego rudasanzwe rwimitsi ya cyclic guanosine monophosphate (cGMP).cGMP ni intumwa ya kabiri ihuza ibisubizo bitandukanye bya selile, nka chloride na bicarbonate isohoka, kuruhura imitsi neza, no guhindura ububabare.Linaclotide ikorera mu gice cya gastrointestinal, kandi ntabwo yinjira mu nzitizi y'amaraso n'ubwonko cyangwa ngo igire ingaruka kuri sisitemu yo hagati.Linaclotide kandi itanga metabolite ikora, MM-419447, ifite imiti isa na linaclotide.Linaclotide na metabolite byombi birwanya kwangirika kwa proteolyique na enzymes zo munda, kandi bikurwaho cyane cyane bidahindutse mumyanda (MacDonald et al., Ibiyobyabwenge, 2017).

Mugukoresha reseptor ya GC-C, linaclotide yongerera ururenda rwamazi mumyanya mara, yoroshya intebe kandi ikorohereza amara.Linaclotide igabanya kandi hyperensitivite ya visceral hamwe no gutwika bifitanye isano na syndrome de munda (IBS) hamwe nizindi ndwara zifata gastrointestinal.Linaclotide ihindura imikorere ya sisitemu yo mu nda ya enteric na nociceptors ya colonike, ari na neuron sensor sensor yohereza ibimenyetso byububabare biva munda mu bwonko.Linaclotide igabanya imvugo ya genes zijyanye n'ububabare, nk'ibintu P na peptide ya calcitonine (CGRP), kandi byongera imvugo ya reseptor ya opioid, ihuza analgesia.Linaclotide kandi igabanya irekurwa rya cytokine itera inflammatory, nka interleukin-1 beta (IL-1β) hamwe na tumorosi ya niyose ya alpha (TNF-α), kandi ikongera irekurwa rya cytokine irwanya inflammatory, nka interleukin-10 (IL -10) no guhindura ibintu bikura beta (TGF-β).Izi ngaruka za linaclotide zitezimbere ibimenyetso byigifu no kubabara munda kubarwayi barwaye IBS cyangwa impatwe idakira (Lembo et al., Ikinyamakuru cyo muri Amerika cyitwa Gastroenterology, 2018).

Linaclotide yerekanwe ko ikora neza kandi yihanganirwa mubigeragezo byinshi byamavuriro birimo abarwayi bafite CC cyangwa IBS-C.Muri ibi bigeragezo, linaclotide yateje imbere amara, nkinshuro yintebe, guhoraho, no kuzura;kugabanya ububabare bwo munda no kutamererwa neza;no kuzamura imibereho yubuzima no guhaza abarwayi.Linaclotide kandi yerekanye umwirondoro mwiza wumutekano, hamwe nimpiswi aribintu bikunze kubaho nabi.Indwara y'impiswi yari iterwa na dose kandi ubusanzwe yoroheje cyangwa igereranije muburemere.Ibindi bintu bibi byabaye mubisanzwe wasangaga umwanya cyangwa hasi muri frequency.Nta bintu bikomeye cyangwa impfu byatewe no kuvura linaclotide (Rao et al., Clinical Gastroenterology na Hepatology, 2015).