title: The effects of enprostil and RS-86505-007 on in-vitro intestinal permeability of rabbit and monkey.
abstract: Enprostil is a prostaglandin E2 analogue characterized as a racemic mixture of four stereoisomers. Enprostil and a single isomer, RS-86505-007, were evaluated for their effects on the permeability of actively and passively transported compounds in segments of small intestine from rabbits and monkeys. Consistent with human in-vivo studies, which have demonstrated decreases in absorption of D-xylose, both compounds inhibited D-glucose transport. The passively transported compounds mannitol and progesterone were also less permeable in this model in the presence of enprostil or RS-86505-007. In contrast to the concentration-dependent inhibition displayed by ouabain, RS-86505-007 had no effect on purified Na+K(+)-ATPase. It is suggested that an effect of a general nature, possibly an increase in the barrier properties at the intestinal surface, may explain the transport inhibition. Of two other enprostil isomers, RS-86812-007 inhibited D-glucose transport in rabbit small intestine, while RS-86505-008 had no effect. The prostaglandin E1 analogue misoprostol was ineffective in monkey and poorly effective in rabbit. This suggests that the inhibition of D-glucose transport by enprostil and its active stereoisomers is mediated through some structurally specific receptor interaction.
authors.affiliation: Institute of Pharmaceutical Sciences, Syntex Research, Palo Alto, CA 94303.
authors.forename: G M
authors.initials: GM
authors.lastname: Grass
authors.forename: S A
authors.initials: SA
authors.lastname: Sweetana
authors.forename: C A
authors.initials: CA
authors.lastname: Bozarth
mesh_terms: D000818:Animals; D016620:Enprostil; D005947:Glucose / Q000493:pharmacokinetics; D066298:In Vitro Techniques; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects*; D008252:Macaca fascicularis; D008297:Male; D008353:Mannitol / Q000493:pharmacokinetics; D010539:Permeability; D011374:Progesterone / Q000493:pharmacokinetics; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D011817:Rabbits; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013237:Stereoisomerism
chemical_list: D011459:Prostaglandins E, Synthetic; D008353:Mannitol; D011374:Progesterone; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose; D016620:Enprostil