Endothelial surface sulfhydryl-groups in blood-brain barrier transport of nutrients.
The sulfhydryl-inhibitors p-chloromercuribenzoic acid (PCMB) and p-chloromercuribenzene sulfonic acid (PCMB-S) were used to study the mechanism of nutrient transport across the blood-brain barrier (BBB) in the rabbit. The vascular endothelium of the left hemisphere was exposed to these agents at 10(-4) M concentration for 35 sec by intracarotid perfusion. The non-perfused right hemisphere served as intact control. 3H-methyl-O-glucose, 14C-cycloleucine and L-DOPA were used as tracers for carrier-mediated nutrient transport, and 3H-norepinephrine, 14C-sucrose and horseradish peroxidase were given to demonstrate abnormal extravasation. Assays of symmetrical samples from left and right hemispheres showed that PCMB-S reduced the uptake of cycloleucine and methylglucose in the perfused hemisphere down to 14.1 +/- 2.3% and 33.2 +/- 2.2%, respectively, without deranging the barrier to the other tracers. PCMB also diminished the uptake of the nutrient tracers, but simultaneously induced extravasation of the normally barred tracers, an effect similar to that induced by mercuric ions in corresponding earlier studies. Our findings indicate that sulfhydryl-groups located on the surface of the luminal membrane of the brain endothelial cells, where they are accessible to PCMB-S binding, are essential for the blood-brain barrier transport of important nutrients.