CHOLINE/ORPHAN V8-2-1/CREATINE TRANSPORTER MESSENGER-RNA IS EXPRESSED IN NERVOUS, RENAL AND GASTROINTESTINAL SYSTEMS

Several cDNAs with substantial sequence homologies to members of the neurotransmitter transporter gene family currently remain 'orphan' transporters, without clearly-identified substrates. We were concerned that a cDNA 'V8-2-1' isolated from a ventral midbrain cDNA library in this laboratory and a virtually-identical cDNA 'CHOT1' reported by Mayser et al. [J. Neurochem., 20 (1973) 581-593] might represent such an orphan. Despite initial reports that it could mediate some choline uptake; neither CHOT1 nor V8-2-1 was demonstrated to confer pharmacologically appropriate choline uptake not already present in either Xenopus oocytes or COS cells. Determination of the regional and tissue-specific distribution of mRNA hybridizing with V8-2-1 cDNA was undertaken to aid in identifying its function. Examination of the distribution of V8-2-1 expression reveals several novel features of this transporter gene family member's distribution, including several features that add to current evidence suggesting that the clone may not encode the classical pharmacologically-defined, hemicholinium-3 sensitive high affinity transporter of cholinergic neurons. This data fits with and extends recent data that suggest that this cDNA represent creatine transporter, and provides initial documentation of his regional distribution in brain.