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Kinetics of circulating vasopressin uptake by choroid plexus
B V Zlokovic1, M B Segal, J G McComb
1Division of Neurosurgery, Children's Hospital of Los Angeles, California.
Abstract:
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.
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