Bidirectional saturable transport of LHRH across the blood-brain barrier.
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)
Barrera
C M
CM
Veterans Affairs Medical Center, New Orleans, Louisiana.
Kastin
A J
AJ
Fasold
M B
MB
Banks
W A
WA
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000502:physiology*; D002339:Carotid Arteries / Q000502:physiology*; D002540:Cerebral Cortex / Q000502:physiology; D002552:Cerebral Ventricles / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D007276:Injections, Intraventricular; D007457:Iodine Radioisotopes; D007700:Kinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D007457:Iodine Radioisotopes; D007987:Gonadotropin-Releasing Hormone