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 physi ological concentrations (0.1 nmol/l), with either L-[H-3]tyrosine or L -[H-3]valine, induced changes in the kinetic parameters of the blood-t o-brain transfer of both large neutral amino acids (LNAA) without alte rations in brain haemodynamics. The half-saturation constant (K-m), th e maximum velocity of transport (V-max) and K-d, the nonsaturable tran sport constant, were estimated in 9 brain regions of male Wistar rats anaesthetized with ether. Apart from K-d, significant changes in K-m a nd V-max were observed in all brain regions investigated. On average K -m 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/mi n/g for tyrosine, and from 29 to 3.2 nmol/min/g for valine, respective ly. The results provide further evidence that vasopressin-receptor int eractions at the blood-brain barrier (BBB) induce changes in the prope rties of the common transporter, the L-system, which eventually result in a suppression of the blood-to-brain transfer of LNAA. Data analysi s of the 5 LNAA tested so far reveals a significant negative correlati on (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 contributio n for each single LNAA to the total influx across the BBB.