Arginine vasopressin reduces the blood-brain transfer of L-tyrosine and L-valine: further evidence of the effect of the peptide on the L-system transporter at the blood-brain barrier.
Arginine vasopressin (AVP) coinjected into the carotid artery in physiological concentrations (0.1 nmol/l), with either L-[3H]tyrosine or L-[3H]valine, induced changes in the kinetic parameters of the blood-to-brain transfer of both large neutral amino acids (LNAA) without alterations in brain haemodynamics. The half-saturation constant (Km), the maximum velocity of transport (V(max)) and Kd, the nonsaturable transport constant, were estimated in 9 brain regions of male Wistar rats anaesthetized with ether. Apart from Kd, significant changes in Km and V(max) were observed in all brain regions investigated. On average Km decreased from 0.17 to 0.048 mmol/l for tyrosine, and from 0.61 to 0.059 mmol/l for valine, whereas V(max) declined from 22 to 9.9 nmol/min/g for tyrosine, and from 29 to 3.2 nmol/min/g for valine, respectively. The results provide further evidence that vasopressin-receptor interactions at the blood-brain barrier (BBB) induce changes in the properties of the common transporter, the L-system, which eventually result in a suppression of the blood-to-brain transfer of LNAA. Data analysis of the 5 LNAA tested so far reveals a significant negative correlation (R = 0.98, P < 0.05) between the respective substrate affinity for the transporter and the corresponding magnitude of transport reduction induced by circulating AVP. Calculations of the unidirectional influx (J) of the LNAA indicate that AVP (1) reduces J by approximately one-third for every LNAA, but (2) does not change the relative contribution for each single LNAA to the total influx across the BBB.
Reichel
A
A
Section of Biosciences, University of Leipzig, Germany.
Begley
D J
DJ
Ermisch
A
A
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014443:Tyrosine / Q000378:metabolism*; D014633:Valine / Q000378:metabolism*
D001127:Arginine Vasopressin; D014443:Tyrosine; D014633:Valine