The human OCTN1 (SLC22A4) reconstituted in liposomes catalyzes acetylcholine transport which is defective in the mutant L503F associated to the Crohn's disease.

摘要: Abstract The organic cation transporter (OCTN1) plays key roles in transport of selected cations, but understanding its biological functions remains limited by restricted knowledge substrate targets. Here we show capacity human OCTN1-reconstituted proteoliposomes to mediate uptake and efflux [ 3 H]acetylcholine, the Km being 1.0 mM with V max 160 nmol⋅mg − 1  protein⋅min . OCTN1-mediated this neurotransmitter was time-dependent stimulated intraliposomal ATP. operates as uniporter translocates acetylcholine both directions. H]acetylcholine competitively inhibited tetraethylammonium, γ-butyrobetaine acetylcarnitine, also various polyamines. Decreasing ATP concentrations increased OCTN for acetylcholine, unaffected. Evaluation properties a variant form OCTN1, Crohn's disease-associated 503F variant, revealed time course, be comparable that wild-type OCTN1. OCTN1 species, 503F-mediated (1.9 nmol⋅mg ) significantly lower than (14 nmol⋅mg ). These data identify new role raise possibility involvement non-neuronal system may relevant pathogenesis disease.