title: Interactions of sodium pentobarbital with D-glucose and L-sorbose transport in human red cells.
abstract: Pentobarbital acts as a mixed inhibitor of net D-glucose exit, as monitored photometrically from human red cells. At 30 degrees C the Ki of pentobarbital for inhibition of Vmax of zero-trans net glucose exit is 2.16+/-0.14 mM; the affinity of the external site of the transporter for D-glucose is also reduced to 50% of control by 1. 66+/-0.06 mM pentobarbital. Pentobarbital reduces the temperature coefficient of D-glucose binding to the external site. Pentobarbital (4 mM) reduces the enthalpy of D-glucose interaction from 49.3+/-9.6 to 16.24+/-5.50 kJ/mol (P<0.05). Pentobarbital (8 mM) increases the activation energy of glucose exit from control 54.7+/-2.5 kJ/mol to 114+/-13 kJ/mol (P<0.01). Pentobarbital reduces the rate of L-sorbose exit from human red cells, in the temperature range 45 degrees C-30 degrees C (P<0.001). On cooling from 45 degrees C to 30 degrees C, in the presence of pentobarbital (4 mM), the Ki (sorbose, glucose) decreases from 30.6+/-7.8 mM to 14+/-1.9 mM; whereas in control cells, Ki (sorbose, glucose) increases from 6.8+/-1.3 mM at 45 degrees C to 23.4+/-4.5 mM at 30 degrees C (P<0.002). Thus, the glucose inhibition of sorbose exit is changed from an endothermic process (enthalpy change=+60.6+/-14.7 kJ/mol) to an exothermic process (enthalpy change=-43+/-6.2 7 kJ/mol) by pentobarbital (4 mM) (P<0.005). These findings indicate that pentobarbital acts by preventing glucose-induced conformational changes in glucose transporters by binding to 'non-catalytic' sites in the transporter.
authors.affiliation: Physiology Group, Biomedical Sciences Division, King's College London, Strand, London WC2R 2LS, UK. richard.naftalin@kcl.ac.uk
authors.forename: R J
authors.initials: RJ
authors.lastname: Naftalin
authors.forename: M
authors.initials: M
authors.lastname: Arain
mesh_terms: D001665:Binding Sites; D001692:Biological Transport; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004912:Erythrocytes / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D010424:Pentobarbital / Q000494:pharmacology*; D013013:Sorbose / Q000378:metabolism*; D013696:Temperature; D013816:Thermodynamics
chemical_list: D009004:Monosaccharide Transport Proteins; D010424:Pentobarbital; D005947:Glucose; D013013:Sorbose