Saturable Retention of Vasopressin by Hippocampus Vessels In Vivo, Associated with Inhibition of Blood‐Brain Transfer of Large Neutral Amino Acids

Abstract

Vasopressin receptors have been reported in the endothelium of brain capillaries. The function of these receptors is not known. To test the prediction that vasopressin receptors in brain capillary endothelium affect amino acid transport across the blood-brain barrier and to assess the role of vasopressin transport across the cerebral vascular endothelium, we measured (a) the endothelial permeability to the large neutral amino acid leucine in the absence and presence of arginine vasopressin (AVP) and (b) the permeability of the blood-brain barrier to AVP relative to manitol. In brain regions protected by the blood-brain barrier, after circulation for 20 s, coinjection of leucine and AVP intravenously led to a decrease of leucine transport unrelated to changes of blood flow. The decrease was most pronounced in hippocampus (42%) and least pronounced in olfactory bulb and colliculi (17 and 19%, respectively). In the latter regions, the endothelial permeability to AVP did not significantly exceed that of mannitol. In hippocampus and in regions with no blood-brain barrier (pituitary and pineal glands), AVP retention in excess of mannitol retention was blocked by unlabeled AVP. The findings do not contradict the hypothesis of a role for AVP in the regulation of large neutral amino acid transfer into brain tissue.

6-[18F]fluoro-l-DOPA Metabolism in Living Human Brain: A Comparison of Six Analytical Methods

“…The transporter is nearly saturated and competitors in plasma inhibit the transport of both labeled compounds (Leenders et a!. , 1986b;Gjedde and Bodsch, 1987;Reith et a!. , 1987) .…”

Effects of Vasopressin on Blood‐Brain Transfer of Methionine in Dogs

“…Prcvious studies have shown that intracarotid or intravenous administration of VP to rats decrease the transport across the BBB of the LNAAs L-leucine and L-phenylalaninc (Brust, 1986;Reith et al, 1987;Brust and Diemer, 1990). By using a noninvasive technique to study BBB transport of amino acids, we examined thc cffccts of VP on ["Clmethioninc transport into thc brain of adult mongrel dogs.…”

“…Other techniques, e g , the intravenous injection methods (Baiios ct al., 1975;Gjedde et al, 1980;Mans el al., 1982), do not permit the separate evaluation of the PSproduct ofindividual amino acids (however, see also Gjedde and Bodsch, 1987). Effccts of AVP on BBB amino acid transport were dcmonstrated in rats using both thc carotid injection tcchnique (Brust, 1986;Brust and Zicha, 1988) and the intravenous injection or intcgral method (Reith et al, 1987;Brust and Diemer, 1990).…”

“…Hormonal regulation of amino acid transport occurs in different cells and tissues (Shotwell et al, 1983). Recently, several studies have shown that the transport of L-leucine and L-phenylalanine from blood to brain is decreased after peripheral administration of the peptide hormone vasopressin (VP) (Brust, 1986;Reith et al, 1987;Brust and Diemer, 1990). Transport was also elevated in rats with congenital VP deficiency (Brust and Zicha, 1988).…”

“…Intracerebrd injection of VP did not affect the blood-brain transfer of amino acids (Brust and Diemer, 1990), but it decreased the extracellular concentrations of taurine and phosphoethanolamine, which may be involved in brain osmoregulation (Brust et al, 1992). There is strong evidence that peripheral VP exerts its effects on the large neutral amino acid (LNAA) transporter of the blood-brain barrier (BBB) by binding to receptors located at the luminal surface of brain endothelial cells (Lerner, 1978;Kretzschmar et al, 1986;Reith et al, 1987;Brust and Diemer, 1990).…”