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 I-125-CRH was used in mice. CRH was rapidly transported out of the brain with a half-time disappearance (t(1/2)) of 15 min, much faster than albumin (t(1/2) = 50 min). Kinetic analysis revealed a saturable component with a low maximum velocity (approximate to 0.020 nmol . min(-1) . brain(-1)) and low capacity (Michaelis constant approximate 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.