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Homovanillic acid transport by the spinal cord

From the Membrane Transport Section, Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland (Drs. Kessler and Fenstermacher); Theoretical Statistics and Mathematics Branch, Biometry Division, National Institute of Mental Health, Bethesda, Maryland (Dr. Patlak).

Spinal subarachnoid perfusions of rhesus monkeys were performed to study spinal transport of homovanillic acid in control and probenecid-treated animals. Homovanillic acid enters capillaries within spinal tissue throughout the spinal cord. The mean capillary exchange half-time for homovanillic acid was 19.2 ± 2.8 minutes; probenecid did not affect this value significantly. Despite its polar nature, homovanillic acid crosses cell boundaries easily and equilibrates in a distribution volume (55 percent) approaching the total water space. The spinal cord clears homovanillic acid from 21 ± 4 µl per minute of cerebrospinal fluid. The rate of clearance after probenecid administration was not significantly different. The apparent diffusion coefficient in tissue of homovanillic acid approximated the diffusion coefficient in water (8.0 ± 10-^–6 cm² per second). The data show that homovanillic acid is transported by capillaries throughout spinal tissue by a mechanism largely insensitive to inhibition by probenecid. Lumbar cerebrospinal fluid concentrations of homovanillic acid even after probenecid administration therefore reflect only part of the total dopamine metabolism.

Requests for reprints should be addressed to Dr. Kessler, Department of Neurology, New York Hospital-Cornell University Medical Center, 525 E. 68th Street, New York, NY 10021.

Portions of this work have been presented to the twenty-seventh annual meeting of the American Academy of Neurology, Bal Harbour, Florida, May 1975.

Received for publication June 17, 1975.