Permeation patterns of polar nonelectrolytes across the guinea pig biliary tree

The biliary permeation of polar nonelectrolytes was studied in anesthetized, bile duct-cannulated guinea pigs with functional cholecystectomy and nephrectomy. During spontaneous secretion, the steady-state bile-to-plasma ratio (B/P) of [14C]urea, [14C]erythritol, [14C]mannitol, [3H]sucrose, and [3H]inulin was 1.02, 0.90, 0.38, 0.12, and 0.04, respectively. Differently structured hydroxy bile acids, but not taurodehydrocholate, reversibly diminished [14C]erythritol and [14C]mannitol B/P during choleresis, and with some of them, particularly taurocholate and glycochenodeoxycholate, the biliary clearance of either solute declined below precholeretic levels. For any given hydroxy bile acid, the degree of B/P diminution was directly related to the molecular radii of these two inert carbohydrates. All bile acids failed to decrease [14C]urea, [3H]sucrose, and [3H]inulin B/P. On the contrary, most of them irreversibly increased [3H]sucrose and [3H]inulin permeability. These results suggest that in the guinea pig 1) hydroxy bile acids diminish the size or rearrange the architecture of the canalicular membrane "aqueous pores" through which [14C]erythritol and [14C]mannitol enter the canaliculus, and 2) solutes of the size of or smaller than [14C]mannitol enter bile primarily through a transcellular route, whereas [3H]sucrose, and [3H]inulin permeate mainly via a transjunctional shunt pathway. These studies indicate that [14C]erythritol and [14C]mannitol cannot be used to estimate canalicular bile flow in this species.