Kinetics of circulating vasopressin uptake by choroid plexus

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.