AJP - Renal Physiology, Vol 260, Issue 2 216-F224, Copyright © 1991 by American Physiological Society
Kinetics of circulating vasopressin uptake by choroid plexus
B. V. Zlokovic, M. B. Segal, J. G. McComb, S. Hyman, M. H. Weiss and H. Davson
Division of Neurosurgery, Children's Hospital of Los Angeles, California.
Uptake of circulating arginine vasopressin (AVP) by choroid plexus was
studied by means of the in situ brain perfusion technique in anesthetized
guinea pig and by means of single-circulation paired-tracer dilution
technique in isolated perfused sheep choroid plexus. Kinetic analysis
revealed saturable AVP uptake with Michaelis constant (Km) values of 32 +/-
4 and 31 +/- 5 nM and maximal saturable influx rate (Vmax) of 0.45 +/- 0.06
and 12.1 +/- 0.67 pmol.min-1.g-1 in guinea pig and sheep choroid plexus,
respectively. The peptide fragments AVP-(1-8) and [pGlu4,Cyt6]AVP-(4-9),
the amino acids L-phenylalanine, L-tyrosine, and
2-aminobicyclo(2,2,1)heptane-2-carboxylic acid, and the aminopeptidase
inhibitors Bestatin and bacitracin did not influence hormone kinetics.
However, the V1 antagonist
[(1-beta-mercapto-beta,beta-cyclo-pentamethylenepropionic
acid)-O-methyl-Tyr2]AVP significantly inhibited AVP uptake with inhibitor
constant (Ki) values of 0.19 +/- 0.03 (guinea pig) and 0.07 +/- 0.01 microM
(sheep). The V2 agonist 1-desamino-8-D-AVP and pressinoic acid produced
weak inhibitions only in guinea pig choroid plexus, and Ki/Km ratios
indicated 220 and 310 times lower affinities than for AVP, respectively. It
is suggested that the membrane mechanism responsible for AVP uptake in
choroid plexus has a binding site with properties similar to those of V1
receptor.
