Kinetics and osmoregulation of na+, cl--dependent betaine transporter in rat renal medulla. Moeckel, Gilbert W., Li-Wen Lai, Walter G. Guder, H. Moo Kwon, and Yeong-Hau H. Lien. Department of Medicine, Section of Renal Disease, the Department of Pediatrics, Section of Medical and Molecular Genetics, University of Arizona Health Sciences Center, Tucson, Arizona 85724, Institute of Clinical Chemistry, Bogenhausen Hospital, Munich 81925, Germany, and Division of Nephrology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
APStracts 3:0202F, 1996.
Betaine is one of the major organic osmolytes which accumulate in the renal medulla in response to high extracellular tonicity. Recent studies in MDCK cells have shown that betaine is taken up by a Na+/Cl--dependent transporter located on the basolateral membrane. We demonstrate here the presence of Na+/Cl--dependent betaine transporter(s) in tubule suspensions prepared from the rat outer and inner medulla. The betaine transport activity was 2-3 times higher in the inner medulla when compared with the outer medulla. The removal of Na+ and Cl- reduced betaine uptake in the outer medullary tubules by 86% and 82%, respectively. The betaine uptake was decreased by 39% in hypotonic buffer (189 mOsm), and increased by 82% in hypertonic buffer (545 mOsm), when compared with isotonic buffer (308 mOsm). Kinetic studies of Na+-dependent betaine uptake in the outer medullary tubules revealed a low and a high affinity component, with Km1 of 8.6 mM, Vmax1 of 112 pmol/[mu]g protein/hour, Km2 of 0.141 mM and Vmax2 of 10 pmol/[mu]g protein/hour, respectively. To investigate whether the Na+/Cl--dependent betaine transporter is regulated by tonicity in vivo, its mRNA was quantitated in rat renal cortex, outer and inner medulla using both canine and rat Na+/Cl--dependent betaine transporter cDNA probes. A single band of 3.0 kb was seen in the Northern blots prepared from both outer and inner medulla, but not in the cortex. Water deprivation for 3 days increased the abundance of this mRNA in the outer and inner medulla by 140% and 170%, respectively, but did not affect its expression in the cortex. In conclusion, Na+/Cl--dependent betaine transporter(s) is present in rat outer and inner medulla tubules, and betaine transporter mRNA abundance is regulated by the hydration state in vivo.

Received 7 February 1996; accepted in final form 24 October 1996.
APS Manuscript Number F43-6.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996