Permeability of porcine blood brain barrier to somatostatin analogues

1 Transport of a fluorescent somatostatin analogue (NBD-octreotide) across freshly isolated functionally intact capillaries from porcine brain was visualized by confocal microscopy and quantitated by image analysis. 2 Luminal accumulation of NBD-octreotide showed all characteristics of specific and energy-dependent transport. Steady-state luminal fluorescence averaged 2-3 times cellular fluorescence and was reduced to cellular levels when metabolism was inhibited by NaCN. 3 The accumulation of NBD-octreotide in capillary lumens was inhibited in a concentration-dependent manner by unlabelled octreotide, by verapamil, PSC-833 and cyclosporin A, potent inhibitors of p-glycoprotein, and by leucotriene C-4, a strong modulator of Mrp2. Conversely, unlabelled octreotide reduced luminal accumulation of fluorescent BODIPY-verapanlil oil glycoprotein and of fluorescein-methotrexate, on Mrp2, None of the inhibitors used significantly reduced cellular accumulation of the fluorescent substrates. 4 Together, the data are consistent with octreotide being transported across the luminal membrane of porcine brain capillaries by both P-gp and Mrp2. providing further evidence that both transporters contribute substantially to the active barrier function of this endothelium. British Journal of Pharmacology (2002).