title: A high cholesterol diet blocks the effect of calcium channel blockers on the uptake of sugars in rabbit intestine.
abstract: Two classes of calcium channel blockers, nisoldipine (NIS) and verapamil (VER), alter the intestinal uptake of sugars, and varying the lipid composition of the diet also modifies intestinal transport function. This study was undertaken in adult male New Zealand rabbits to assess the effect of 3 weeks of dosing with NIS (1 mg.kg-1.day-1) or VER (4 mg.kg-1.day-1) on the in vitro jejunal uptake of D-galactose and L- or D-glucose. The value of the maximal transport rate of D-galactose (Vmax) increased with NIS and VER, compared with control vehicle. The value of the apparent Michaelis constant (K(m)) rose with NIS and fell with VER, and the value of the passive permeability coefficient (Pd) estimated from the uptake of L-glucose fell with NIS and rose with VER. These effects of NIS and VER on Vmax, K(m), and Pd were prevented by feeding a high cholesterol (2.8%) supplemented chow diet (HCD), as compared with chow alone. These effects were not due to any change in the animal's weight gain or intestinal mucosal surface area. The acute exposure of the jejunal tissue in vitro to varying concentrations of NIS but not VER reduced the uptake of D-glucose but had no effect on basal short circuit current (Isc) in either chow or HCD. Isc stimulated with glucose or theophylline was less in chow-fed rabbits compared with HCD-fed rabbits given NIS or VER. Thus, the active transport of sugars by the sodium-dependent transporter in the brush-border membrane, SGLT1, and the passive uptake by the paracellular route are variably influenced by these two classes of calcium channel blockers, and this effect is modified by the cholesterol content of the diet.
authors.affiliation: Division of Gastroenterology, University of Alberta, Edmonton, Canada.
authors.forename: D H
authors.initials: DH
authors.lastname: Hyson
authors.forename: A B
authors.initials: AB
authors.lastname: Thomson
authors.forename: M
authors.initials: M
authors.lastname: Keelan
authors.forename: C T
authors.initials: CT
authors.lastname: Kappagoda
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002241:Carbohydrates / Q000493:pharmacokinetics*; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005947:Glucose / Q000494:pharmacology; D007408:Intestinal Absorption / Q000187:drug effects*; D007583:Jejunum / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D015737:Nisoldipine / Q000493:pharmacokinetics*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011817:Rabbits; D013806:Theophylline / Q000494:pharmacology; D014700:Verapamil / Q000493:pharmacokinetics*
chemical_list: D002121:Calcium Channel Blockers; D002241:Carbohydrates; D002791:Cholesterol, Dietary; D010726:Phosphodiesterase Inhibitors; D015737:Nisoldipine; D013806:Theophylline; D014700:Verapamil; D005947:Glucose