AJP - Endocrinology and Metabolism, Vol 261, Issue 3 E312-E318, Copyright © 1991 by American Physiological Society
Bidirectional saturable transport of LHRH across the blood-brain barrier
C. M. Barrera, A. J. Kastin, M. B. Fasold and W. A. Banks
Veterans Affairs Medical Center, New Orleans, Louisiana.
Systemic administration of luteinizing hormone-releasing hormone (LHRH) in
rats has been found to influence behavior independently of pituitary or
ovarian function. A previous study has shown that LHRH can cross the
blood-brain barrier in one direction, but it was not known whether this was
due to a saturable transport system. The rate of entry of 125I-labeled LHRH
from blood to brain was determined by two different single-pass methods of
carotid perfusion. The first, a multiple time point method, measures Ki
from the slope of the linear regression when brain-to-blood ratios of
radioiodinated LHRH are plotted against time. Saturable transport was
determined by the difference between the Ki of rats perfused with 125I-LHRH
(12.51 X 10(-3) mg.g-1.min-1) vs. rats perfused with 125I-LHRH and
unlabeled LHRH (10 nmol/ml; 2.20 X 10(-3) ml.g-1.min-1). The inhibition by
the unlabeled peptide was statistically significant (P less than 0.001).
The second method, a single time point technique, measures the
cerebrovascular permeability-surface area coefficient (PA). Saturable
transport was determined in rats by the competition of unlabeled LHRH with
125I-LHRH. The PA value for 125I-LHRH (20.00 X 10(-3) ml.g-1.min-1) was
significantly greater (P less than 0.05) than for 125I-LHRH with the
addition of 10 nmol/ml unlabeled LHRH (4.14 X 10(-3) ml.g-1.min-1).
Saturable transport of LHRH from brain to blood in mice was also
determined.(ABSTRACT TRUNCATED AT 250 WORDS)
