Saturable mechanism for delta sleep-inducing peptide (DSIP) at the blood-brain barrier of the vascularly perfused guinea pig brain.
Cellular uptake of [125I] labelled DSIP at the luminal interface of the blood-brain barrier (BBB) was studied in the ipsilateral perfused in situ guinea pig forebrain. Regional unidirectional transfer constants (Kin) calculated from the multiple-time brain uptake analysis were 0.93, 1.33 and 1.66 microliter.min-1 g-1 for the parietal cortex, caudate nucleus and hippocampus, respectively. In the presence of 7 microM unlabelled DSIP the brain uptake of [125I]-DSIP (0.3 nM) was inhibited, the values of Kin being reduced to 0.23-0.38 microliter.min-1 g-1, values that were comparable with the Kin for mannitol. The rapidly equilibrating space of brain, measured from the intercept of the line describing brain uptake versus time on the brain uptake ordinate, Vi, was greater for [125I]-DSIP than for mannitol; in the presence of unlabelled DSIP this was reduced to that of mannitol, and it was suggested that the larger volume for [125I]-DSIP represented binding at specific sites on the brain capillary membrane. L-tryptophan, the N-terminal residue of DSIP, in concentrations of 7 microM and 1 mM, inhibited Kin without affecting Vi. A moderate inhibition of Kin was obtained by vasopressin ([Arg8]-VP), but only at a concentration as high as 0.2 mM. The results suggest the presence of a high affinity saturable mechanism for transport of DSIP across the blood-brain barrier, with subsequent uptake at brain sites that are highly sensitive to L-tryptophan, and may be modulated by [Arg8]-VP.
Zlokovic
B V
BV
Department of Medical Physiology, Faculty of Medicine Belgrade, Yugoslavia.
Susic
V T
VT
Davson
H
H
Begley
D J
DJ
Jankov
R M
RM
Mitrovic
D M
DM
Lipovac
M N
MN
D000818:Animals; D001667:Binding, Competitive; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D002421:Caudate Nucleus / Q000378:metabolism; D002560:Cerebrovascular Circulation; D003701:Delta Sleep-Inducing Peptide / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D006624:Hippocampus / Q000378:metabolism; D007700:Kinetics; D008297:Male; D010296:Parietal Lobe / Q000378:metabolism; D010477:Perfusion; D011956:Receptors, Cell Surface / Q000378:metabolism*
D011956:Receptors, Cell Surface; D003701:Delta Sleep-Inducing Peptide