Fig. 2.
Passive and carrier-mediated BBB fluxes of nicotine. a Total flux (J in; in nanomoles per second per gram; dashed line) measured in the right brain hemispheres of Swiss mice and plotted against total nicotine concentration in the Krebs carbonate perfusion fluid at pHe 7.40. The straight dotted line represents the passive diffusion of nicotine (K d of 3.67 ± 0.14 μl/s/g; for both cationic and neutral forms at pHe 7.40). The solid line represents the curve obtained by subtracting the passive flux from the total flux and fitted to the carrier-mediated Michaelis–Menten equation by nonlinear least squares regression. The estimated parameters are a K m of 2.60 ± 0.19 mM and a V max of 37.60 ± 2.88 nmol/s/g for the brain transport of nicotine. b Total (J in; dashed line), calculated according Eq. 6, and individual passive (dotted line) and carrier-mediated (solid line) nicotine fluxes at the BBB fitted according to each component of Eq. 7 and according to the physiological nicotine concentrations. Data represent the means ± SD of four to eight animals