Transport of lead-203 at the blood-brain barrier during short cerebrovascular perfusion with saline in the rat.
Lead transport at the blood-brain barrier has been studied by short (less than 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 203 Pb-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 microM. Five percent albumin, 200 microM cysteine, or 1 mM 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 mM bicarbonate or 50 microM 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid was without effect. Increasing the potassium concentration reduced 203Pb uptake. Vanadate at 2 mM, 2 microM carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone (a metabolic uncoupler), or 2 microM 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.
Deane
R
R
Department of Physiology, King's College, London, England.
Bradbury
M W
MW
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D001692:Biological Transport; D001812:Blood-Brain Barrier; D002412:Cations / Q000494:pharmacology; D002560:Cerebrovascular Circulation; D004492:Edetic Acid / Q000494:pharmacology; D005260:Female; D006863:Hydrogen-Ion Concentration; D007854:Lead / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007856:Lead Radioisotopes; D009994:Osmolar Concentration; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride; D013997:Time Factors
D001639:Bicarbonates; D002412:Cations; D007856:Lead Radioisotopes; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D007854:Lead; D012965:Sodium Chloride; D004492:Edetic Acid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid