Entry of CART into brain is rapid but not inhibited by excess CART or leptin

Cocaine- and amphetamine-regulated transcript (CART) is a new anorectic pep tide found in the brain and periphery. It is closely associated with leptin , an anorectic agent saturably transported across the blood-brain barrier ( BBB). Using multiple time-regression analysis, we found that CART has a rap id rate of entry into brain from blood. However, there was no self-inhibiti on with CART, even when perfused in blood-free buffer or in fasted mice, sh owing a lack of saturation. HPLC showed that at least 58% of the injected C ART reached brain tissue in intact form, and capillary depletion with and w ithout washout showed that the CART was not bound to endothelial cells or a dherent to vascular components. There was no evidence for an efflux system out of the brain for CART. Thus CART can cross the BBB from blood to brain, but its rapid rate of entry is not inhibited by excess CART or leptin.