Drug uptake into everted intestinal sacs. II. Inhibition of secretion by hypertonicity.
Mucosal hypertonicity, metabolic inhibitors, or absence of glucose and oxygen enhance mucosal-to-serosal influx of the cationic drug, pralidoxime (PAM), into sacs of everted rat jejunum in vitro. Conversely, efflux of PAM, which is twice the influx rate, is inhibited by mucosal hypertonicity or cyanide and iodoacetate. When sacs containing PAM, 0.87 mM, and glucose, 10 mM, were placed in identical drug- and sugar-containing mediums, the inside (serosal) concentration of PAM fell by over half in 120 min, whereas that of glucose more than doubled. Mucosal hypertonicity depressed PAM efflux and glucose influx regardless of serosal osmolarity. Although azide and mucosal hypertonicity each depressed glucose uptake and oxygen consumption while accelerating net PAM influx, azide more effectively depressed glucose and oxygen uptake, whereas hypertonicity caused greater acceleration of PAM uptake. Hypertonicity did not affect PAM binding to intestinal tissue. Varying mucosal pH did not change PAM or glucose uptake. Thus, mucosal hypertonicity apparently enhances net mucosal-to-serosal transfer of PAM by blocking its active secretion from serosa to mucosa.
D000818:Animals; D001386:Azides / Q000494:pharmacology; D003486:Cyanides / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006982:Hypertonic Solutions; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D007461:Iodoacetates / Q000494:pharmacology; D007583:Jejunum / Q000378:metabolism*; D009994:Osmolar Concentration; D010101:Oxygen Consumption; D011220:Pralidoxime Compounds / Q000378:metabolism*; D051381:Rats
D001386:Azides; D003486:Cyanides; D006982:Hypertonic Solutions; D007461:Iodoacetates; D011220:Pralidoxime Compounds; D005947:Glucose