ACUTE MODULATION OF ACTIVE CARRIER-MEDIATED BRAIN-TO-BLOOD TRANSPORT OF CORTICOTROPIN-RELEASING HORMONE

The unidirectional brain-to-blood transport system for corticotropin-r eleasing hormone (CRH) across the blood-brain barrier could be instrum ental in the homeostasis of central CRH. To characterize this system, the intracerebroventricular injection of I-125-CRH was used in mice. C RH was rapidly transported out of the brain with a half-time disappear ance (t(1/2)) of 15 min, much faster than albumin (t(1/2) = 50 min). K inetic analysis revealed a saturable component with a low maximum velo city (approximate to 0.020 nmol . min(-1) . brain(-1)) and low capacit y (Michaelis constant approximate to 1.4 nmol/brain). Transport was in hibited by verapamil, ouabain, and colchicine but not by cyclosporin. Transport was increased by corticosterone and inhibited by tumor necro sis factor-alpha and beta-endorphin. These results suggest that the sp ecific unidirectional brain-to-blood transport system for CRH is depen dent on energy and calcium channels, involves microtubules, is indepen dent of the P-glycoprotein transporter, and is acutely modulated by ad renal steroids, cytokines, and endogenous opiates. This suggests its p articipation in the control of the stress response.