Transport of Lead‐203 at the Blood‐Brain Barrier During Short Cerebrovascular Perfusion with Saline in the Rat

Abstract: Lead transport at the blood‐brain barrier has been studied by short (< 1.5 min) vascular perfusion of one cerebral hemisphere of the rat with a buffered physiological salt solution at pH 7.4 without calcium, magnesium, or bicarbonate and containing 203Pb‐labelled lead chloride. In the absence of complexing agents, 203Pb uptake was rapid, giving a space of 9.7 ml/100 g of wet frontal cortex at 1 min. Lead‐203 influx was linear with lead concentration up to 4 μM. Five percent albumin, 200 μM cysteine, or 1 μM EDTA almost abolished 203Pb uptake. Lead‐203 entry into brain was uninfluenced by varying the calcium concentration or by magnesium or the calcium blocker methoxyverapamil. Similarly, 1 μM bicarbonate or 50 μM 4,4′‐diisothiocyanostilbene‐2,2′‐disulphonic acid was without effect. Increasing the potassium concentration reduced 203Pb uptake. Vanadate at 2 μM, 2 μM carbonyl cyanide 4‐(trifluoromethoxy)phenylhydrazone (a metabolic uncoupler), or 2 μM stannic chloride all markedly enhanced lead entry into brain, as did a more alkaline pH (7.80). In conclusion, there is a mechanism allowing rapid passive transport of 203Pb at the brain endothelium, perhaps as PbOH+. Lead uptake into brain via this system is probably made less important by active transport of lead back into the capillary lumen by the calcium‐ATP‐dependent pump.