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Circulating arginine-vasopressin (AVP) is known to reduce the blood-to-brain transfer of large neutral amino acids (AA). As a first step to examine whether the reduced uptake by brain endothelial cells is reflected in changes in large neutral amino acid levels of the extracellular fluid environment of cells within the nervous tissue, we measured the concentrations of amino acids in plasma, cerebrospinal fluid (CSF), and hippocampal tissue of rats before and after infusion of AVP (34 and 68 ng/min/kg, respectively) over the time period of 60 min. AA levels changed in all compartments investigated during both saline and AVP infusions. Whereas in the saline-infused controls changes in CSF AA levels paralleled those in plasma, this correlation was abolished by raising AVP concentrations. The effect of AVP was found to be i) dependent on the AA, ii) different with respect to direction and iii) magnitude of changes in AA levels, and iv) in some cases dose dependent. In summary, AVP infusion increased plasma levels of 10 AA, but decreased all 15 AA measured by some 30% in CSF. In contrast to CSF, levels of AA were slightly enhanced in the hippocampal tissue. The results are not solely explicable by a reduced blood-to-brain transfer of AA. We conclude that further mechanisms by which AVP affects the availability of AA to the brain may exist. The physiological significance of the findings might be related to brain osmoregulation, especially in situations of stress.

Cellular uptake of [125I] labelled DSIP at the luminal interface of the blood-brain barrier (BBB) was studied in the ipsilateral perfused in situ guinea pig forebrain. Regional unidirectional transfer constants (Kin) calculated from the multiple-time brain uptake analysis were 0.93, 1.33 and 1.66 microliter.min-1 g-1 for the parietal cortex, caudate nucleus and hippocampus, respectively. In the presence of 7 microM unlabelled DSIP the brain uptake of [125I]-DSIP (0.3 nM) was inhibited, the values of Kin being reduced to 0.23-0.38 microliter.min-1 g-1, values that were comparable with the Kin for mannitol. The rapidly equilibrating space of brain, measured from the intercept of the line describing brain uptake versus time on the brain uptake ordinate, Vi, was greater for [125I]-DSIP than for mannitol; in the presence of unlabelled DSIP this was reduced to that of mannitol, and it was suggested that the larger volume for [125I]-DSIP represented binding at specific sites on the brain capillary membrane. L-tryptophan, the N-terminal residue of DSIP, in concentrations of 7 microM and 1 mM, inhibited Kin without affecting Vi. A moderate inhibition of Kin was obtained by vasopressin ([Arg8]-VP), but only at a concentration as high as 0.2 mM. The results suggest the presence of a high affinity saturable mechanism for transport of DSIP across the blood-brain barrier, with subsequent uptake at brain sites that are highly sensitive to L-tryptophan, and may be modulated by [Arg8]-VP.