Blood–brain barrier transport studies of organic guanidino cations using an in situ brain perfusion technique

Blood–brain barrier (BBB) transport of essential polar substrates is mediated by specific, carrier-mediated transport proteins. The BBB transport mechanisms for polar compounds with terminal guanidino functional groups (R–NHC(NH)NH 2) are not well defined. The goal of the present work was to investigate the BBB transport mechanism(s) for terminal guanidino substrates using an in situ brain perfusion technique. Brain region radiotracer influx clearance (Cl in) was calculated for representative guanidino substrates, [ 14C] l-arginine, [ 14C]aminoguanidine and [ 14C]guanidine, in the presence or absence of excess terminal guanidino analogues. The Cl in for [ 14C] l-arginine (0.21±0.0094 cm 3/min/g wet brain weight, mean±S.E.M., n=four rats) was significantly decreased by 1000× concentrations of unlabeled l-arginine, N G-methyl- l-arginine, N G-, N G-dimethyl- l-arginine and N G-amino- l-arginine by ∼83% ( P