Na(+)/Cl(-)/creatine transporter activity and expression in rat brain synaptosomes

Creatine is involved in brain ATP homeostasis and it may also act as neurotransmitter. Creatine transport was measured in synaptosomes obtained from the diencephalon and telencephalon of suckling and 2 month-old rats. Synaptosomes accumulate [(14)C]-creatine and this accumulation was Na(+)- and Cl(-)-dependent and inhibited by high external K(+). The latter suggests that the uptake process is electrogenic. The kinetic study revealed a K(m) for creatine of 8.7 microM. A 100-fold excess of either non-labelled creatine or guanidinopropionic acid abolished NaCl/creatine uptake, whereas GABA uptake was minimally modified, indicating a high substrate specificity of the creatine transporter. The levels of NaCl/creatine transporter (CRT) activity and those of the 4.2 kb CRT transcript (Northern's) were higher in the diencephalon than in the telencephalon, whereas the 2.7 kb transcript levels were similar in both brain regions and lower than those of the 4.2 kb. These observations suggest that the 4.2 kb transcript may code for the functional CRT. CRT activity and mRNA levels were similar in suckling and adult rats. To our knowledge the current results constitute the first description of the presence of a functional CRT in the axon terminal membrane that may serve to recapture the creatine released during the synapsis.