Brain gamma-glutamyltranspeptidase: Characteristics, development and thyroid hormone dependency of the enzyme in isolated microvessels and neuronal/glial cell plasma membranes
Sj. Hemmings et Kb. Storey, Brain gamma-glutamyltranspeptidase: Characteristics, development and thyroid hormone dependency of the enzyme in isolated microvessels and neuronal/glial cell plasma membranes, MOL C BIOCH, 202(1-2), 1999, pp. 119-130
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.