RGD Reference Report - Polyspecific cation transporters mediate luminal release of acetylcholine from bronchial epithelium. - Rat Genome Database

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Polyspecific cation transporters mediate luminal release of acetylcholine from bronchial epithelium.

Authors: Lips, KS  Volk, C  Schmitt, BM  Pfeil, U  Arndt, P  Miska, D  Ermert, L  Kummer, W  Koepsell, H 
Citation: Lips KS, etal., Am J Respir Cell Mol Biol. 2005 Jul;33(1):79-88. Epub 2005 Apr 7.
RGD ID: 2317432
Pubmed: PMID:15817714   (View Abstract at PubMed)
DOI: DOI:10.1165/rcmb.2004-0363OC   (Journal Full-text)

In airway epithelia, non-neuronal cholinergic regulations have been described; however, the route for acetylcholine (ACh) release has not been verified. To investigate whether organic cation transporters (OCTs) serve this function, we studied the expression of OCTs in airway epithelia and their capability to translocate ACh. Using immunohistochemistry in rats and humans, OCT1, OCT2, and OCT3 were localized to the luminal membrane of ciliated epithelial cells. In humans, OCT2 showed the strongest expression in the luminal membrane. We expressed the OCT isoforms in oocytes of Xenopus laevis and measured uptake and efflux of ACh. Tracer flux measurements showed that ACh is transported by OCT1 and OCT2 but not by OCT3. Two-electrode-voltage-clamp measurements revealed that OCT2 mediates electrogenic uptake and efflux of ACh. For ACh uptake by human OCT2, a K(M) value of approximately 0.15 mM was determined. At -50 mV, ACh efflux by human OCT2 was trans-inhibited by micromolar concentrations of the inhalational glucocorticoid budesonide, which is used in treatment of asthma (K(i) approximately 2.7 microM). The data show that OCT1 and OCT2 mediate luminal ACh release in human airways and suggest that ACh release is blocked after inhalation of budesonide.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc22a1Ratacetylcholine transport involved_inIDA PMID:15817714UniProt 
Slc22a2Ratacetylcholine transport involved_inIDA PMID:15817714UniProt 
Slc22a1Ratestablishment or maintenance of transmembrane electrochemical gradient  IDA  RGD 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Slc22a1Ratapical plasma membrane located_inIDA PMID:15817714UniProt 
Slc22a2Ratapical plasma membrane located_inIDA PMID:15817714UniProt 
Slc22a3Ratapical plasma membrane located_inIDA PMID:15817714UniProt 

Molecular Function

  

Objects Annotated

Genes (Rattus norvegicus)
Slc22a1  (solute carrier family 22 member 1)
Slc22a2  (solute carrier family 22 member 2)
Slc22a3  (solute carrier family 22 member 3)


Additional Information