TRANSPORT OF ZN-65 AT THE BLOOD-BRAIN-BARRIER DURING SHORT CEREBROVASCULAR PERFUSION IN THE RAT - ITS ENHANCEMENT BY HISTIDINE

Zinc-65 transport into different regions of rat brain has been measure d during short vascular perfusion of one cerebral hemisphere with an o xygenated HEPES-containing physiological saline at pH 7.40. The [Zn2+] was buffered with either bovine serum albumin or histidine. In each c ase uptake was linear with time up to 90 s. Zn-65 flux into brain in t he presence of albumin followed Michaelis-Menten kinetics and for pari etal cortex had a K-m of 16 nM and a V-max of 44 nmol/kg/min. Increasi ng concentrations of L-histidine enhanced Zn-65 flux into brain at [Zn 2+] values between 1 and 1,000 nM. The combined effect of [histidine] and [Zn2+] was best accounted for by a function of [ZnHis(+)], i.e., f lux = 64.4 [ZnHis(+)]/(390 + [ZnHis(+)]) + 0.00378 [ZnHis(+)], with co ncentrations being nanomolar. D-Histidine had an influence similar to that of L-histidine. Zn-65 flux in the presence of 100 mu M L-histidin e was not affected by either 500 mu M L-arginine or 500 mu M L-phenyla lanine. The results indicate specific transport of Zn2+ across the pla sma membranes of brain endothelium. The enhancement due to histidine h as been attributed to diffusion of ZnHis(+) across unstirred layers '' ferrying'' zinc to and from transport sites.