Acute modulation of the active carrier-mediated brain to blood
transport of corticotropin-releasing hormone.
Martins, J. Martin, William A. Banks, and Abba J. Kastin.
Veterans Affairs Medical Center and Tulane University School of
Medicine, New Orleans, LA 70146
APStracts 3:0204E, 1996.
The unidirectional brain to blood transport system for corticotropin
-releasing hormone (CRH) across the blood-brain barrier could be
instrumental in the homeostasis of central CRH. To characterize this
system, the intracerebroventricular injection of 125I-CRH was used in
mice. CRH was rapidly transported out of the brain with a half-time
disappearance (t1/2) of 15 min, much faster than albumin (t1/2=50
min). Kinetic analysis revealed a saturable component with a low
maximum velocity (Vmax nearly equal to 0.020 nmol/min.brain) and low
capacity (Km nearly equal to 1.4 nmol/brain). Transport was inhibited
by verapamil, ouabain, and colchicine but not by cyclosporin.
Transport was increased by corticosterone and inhibited by tumor
necrosis factor-[alpha] and [beta]-endorphin. These results suggest
that the specific unidirectional brain to blood transport system for
CRH is dependent on energy and calcium channels, involves
microtubules, is independent of the p-glycoprotein transporter, and
is acutely modulated by adrenal steroids, cytokines, and endogenous
opiates, This suggests its participation in the control of the stress
response.
Received 17 July 1996; accepted in final form 4 October 1996.
APS Manuscript Number E341-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 5 November 1996