Role of carboxyl group in Na+-entry step at apical membrane of toad urinary bladder.
Mucosal addition of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) and some lipid-soluble carbodiimides, agents which are selective for carboxyl groups, irreversibly inhibited Na+ transport as measured by short-circuit current (SCC) in the urinary bladder of the toad. The inhibition of Na+ transport by EEDQ had the following characteristics: 1) the inhibition was accompanied by a significant increase in the transepithelial electrical resistance; 2) the decrease in SCC was accounted for by a comparable decrease in 22Na+ influx without effect on Na+ efflux; 3) amphotericin B produced complete recovery of SCC inhibited with EEDQ but not with antimycin A or ouabain; 4) mucosal EEDQ decreased the amiloride-sensitive reversal of Na+ current that is induced by serosal nystatin in the absence of mucosal Na+; 5) vasopressin and acid mucosal pH caused an increase in SCC in proportion to the SCC remaining after EEDQ inhibition; and 6) Vmax of the SCC was decreased without alteration in the apparent Km for Na+. Based on these characteristics of EEDQ inhibition of Na+ transport, we infer that a carboxyl group of the Na+ channel is involved in the Na+-entry step across the apical membrane of "tight" epithelia. The inhibition of Na+ transport with EEDQ most likely involves closing the Na+ channel through a chemical reaction involving a carboxyl group of the channel.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002024:Bufo marinus; D002234:Carbodiimides / Q000494:pharmacology*; D004553:Electric Conductivity; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D007700:Kinetics; D009092:Mucous Membrane / Q000187:drug effects / Q000502:physiology; D009761:Nystatin / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D001743:Urinary Bladder / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D002234:Carbodiimides; D011804:Quinolines; D009761:Nystatin; C000470:EEDQ; D012964:Sodium