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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Scalise, Mariafrancesca Pani, Giovambattista Indiveri, Cesare Pochini, Lorena Siminovitch, Katherine A. Galluccio, Michele |
| Description | Author Affiliation: Pochini L ( Department of Cell Biology, University of Calabria, Arcavacata di Rende, Italy.) |
| Abstract | The organic cation transporter (OCTN1) plays key roles in transport of selected organic cations, but understanding of its biological functions remains limited by restricted knowledge of its substrate targets. Here we show capacity of human OCTN1-reconstituted proteoliposomes to mediate uptake and efflux of [ $^{3}$ H]acetylcholine, the Km of transport being 1.0 mM with V $_{max}$ of 160 nmol⋅mg $^{−$ 1 protein⋅min $^{−$ 1 . OCTN1-mediated transport of this neurotransmitter was time-dependent and was stimulated by intraliposomal ATP. The transporter operates as uniporter but translocates acetylcholine in both directions. [ $^{3}$ H]acetylcholine uptake was competitively inhibited by tetraethylammonium, γ-butyrobetaine and acetylcarnitine, and was also inhibited by various polyamines. Decreasing intraliposomal ATP concentrations increased OCTN Km for acetylcholine, but V $_{max}$ was unaffected. Evaluation of the acetylcholine transporter properties of a variant form of OCTN1, the Crohn's disease-associated 503F variant, revealed time course, Km and V $_{max}$ for acetylcholine uptake to be comparable to that of wild-type OCTN1. Km for acetylcholine efflux was also comparable for both OCTN1 species, but V $_{max}$ of OCTN1 503F-mediated acetylcholine efflux (1.9 nmol⋅mg $^{−$ 1 protein⋅min $^{−$ 1 ) was significantly lower than that of wild-type OCTN1 (14 nmol⋅mg $^{−$ 1 protein⋅min $^{−$ 1 ). These data identify a new transport role for OCTN1 and raise the possibility that its involvement in the non-neuronal acetylcholine system may be relevant to the pathogenesis of Crohn's disease. |
| ISSN | 00063002 |
| Journal | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer |
| Issue Number | 3 |
| Volume Number | 1818 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2012-03-01 |
| Publisher Place | Netherlands |
| Access Restriction | Open |
| Subject Keyword | Acetylcholine Chemistry Amino Acid Substitution Crohn Disease Liposomes Mutation, Missense Organic Cation Transport Proteins Acetylcarnitine Pharmacology Genetics Metabolism Adenosine Triphosphate Betaine Analogs & Derivatives Biological Transport, Active Carnitine Catalysis Kinetics Nootropic Agents Antagonists & Inhibitors Potassium Channel Blockers Tetraethylammonium Research Support, Non-U.S. Gov't Biochemistry |
| Content Type | Text |
| Resource Type | Article |
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