A NA-DEPENDENT CREATINE TRANSPORTER IN RABBIT BRAIN, MUSCLE, HEART, AND KIDNEY - CDNA CLONING AND FUNCTIONAL EXPRESSION()

A cDNA has been cloned from rabbit brain that is a new member of the e merging family of Na+-dependent plasma membrane transporters for sever al neurotransmitters and structurally related compounds. Functional ex pression of this cDNA in COS-7 cells identifies its product as a Na+- and Cl--dependent creatine transporter with a K(m) of approximately 35 muM. Its creatine transporter activity is efficiently antagonized by 3-guanidinopropionate, a well characterized alternative substrate of c reatine transport in several tissues, and by 4-guanidinobutyrate. More distant structural analogues of creatine are much less efficient or i nactive as antagonists, indicating a high substrate specificity of the transporter. Northern blot hybridization detects the expression of it s mRNA in most tissues tested, most prominently in kidney, heart, and muscle, but not in liver and intestine. A full-length cDNA clone was a lso isolated from a muscle cDNA library and found to contain the same coding sequence. Substrate affinity and specificity of the cloned tran sporter are very similar to the endogenous creatine transporter of the COS-7 cells and to the creatine transport activities of several cell types described in the literature. Moreover, its mRNA is most abundant in the tissues known to possess high creatine uptake capacity.