Acute modulation of active carrier-mediated brain-to-blood transport of corticotropin-releasing hormone.
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 (apaproximately 0.020 nmol x min(-1) x brain(-1)) and low capacity (Michaelis constant approximately 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.
Martins
J M
JM
Veterans Affairs Medical Center and Tulane University School of Medicine, New Orleans, Louisiana 70146, USA.
Banks
W A
WA
Kastin
A J
AJ
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000097:blood / Q000493:pharmacokinetics*; D016207:Cytokines / Q000494:pharmacology; D006801:Humans; D009075:MSH Release-Inhibiting Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats; D001615:beta-Endorphin / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D002352:Carrier Proteins; D016207:Cytokines; D001615:beta-Endorphin; C036930:tyrosyl-prolyl-leucyl-glycinamide; D003346:Corticotropin-Releasing Hormone; D009075:MSH Release-Inhibiting Hormone