Brain gamma-glutamyltranspeptidase: Characteristics, development and thyroid hormone dependency of the enzyme in isolated microvessels and neuronal/glial cell plasma membranes

The characteristics, cellular locus and regulation of the enzyme gamma-glut amyltranspeptidase (gamma GT) in brain were examined. In rat brain homogena tes, the activity of the enzyme exhibited tissue differences - kidney>>>bra in==testis>>liver>>skeletal muscle = ventricular muscle and regional differ ences - brain stem>hippocampus = cerebellum>cerebral cortex, with no signif icant species/strain differences in the select group of mammals studied. Me thods were developed for the isolation from brain of microvessels (MV) and plasma membranes from neuronal/glial cells (N/G PM) utilizing morphological indicators and marker analyses. gamma GT activity was >12 higher in MV tha n N/G PM; however the enzyme displayed: stability, heat-activation and inhi bition with maleate to the same extent in both fractions. A comparative stu dy indicated that in the N/G PM fraction, gamma GT activity was low in all animals studied; gamma GT activity in MV however, was barely detectable in amphibians and reptiles, very low in birds and very high in mammal - mirror ing the phylogenetic development of a functional blood-brain barrier. In th e rat, gamma GT in both MV and N/G PM displayed a pronounced postnatal incr ease in activity but the extent and the patterns were different - in all ca ses, that of the MV greatly exceeded that of the N/G PM and in the MV, the enzyme activity the exhibited the same pattern as the postnatal development of the blood-brain barrier. The induction of congenital hypothyroidism by propylthiouracil (PTU) had no effect on gamma GT in N/G PM but effected a o ne third reduction in the activity of gamma GT in MV. The normalization by thyroid hormone replacement indicated that MV gamma GT is under thyroid hor mone control. The induction of hypothyroidism by PTU in the adult, however, was without effect on enzyme activity in either fraction. The implications of the thyroid hormone dependency of MV gamma GT in the neonatal period an d the relationship of gamma GT to the function of the blood brain-barrier i s discussed.