The role of nitric oxide in the regulation of macromolecular transport in rat jejunum.
1. Nitric oxide is known to affect epithelial and microvascular permeability and is a major non-adrenergic non-cholinergic neurotransmitter in the intestine. We have previously demonstrated neuronal regulation of macromolecular transport in the intestine. To define this regulation further the role of nitric oxide was investigated. 2. Stripped rat jejunum was mounted in Ussing chambers exposing the mucosal surface to bovine serum albumin (BSA; 2 mg ml-1), or BSA (2 mg ml-1) plus [125I]BSA (10 microCi). Following a 50 min equilibration, serosal fluids were sampled for four 10 min periods, and fluxes determined for intact BSA by enzyme-linked immunosorbent assay (ELISA) and total BSA by [125I]BSA under basal conditions, and after treatment with NG-nitro-L-arginine-methyl ester (L-NAME) alone or in conjunction with L-arginine or decarboxylated molsidomine (SIN 1). 3. L-NAME significantly increased intact BSA uptake. Total (intact + degraded) BSA flux was not altered. The L-NAME effect was reversed by L-arginine and SIN 1. Additional experiments were performed by adding the nitric oxide donors sodium nitroprusside and SIN 1 directly to control tissue. Nitric oxide donors did not further decrease intact BSA flux below levels obtained from control tissue. The L-NAME enantiomer D-NAME had no effect. Sodium-free bathing solutions also had no effect on intact BSA uptake. Non-specific permeability, as assessed by the serosal to mucosal movement of [51Cr]ethylene-diamine-tetraacetate ([51Cr]EDTA), was decreased with L-NAME. 4. The findings indicate that nitric oxide downregulates intact macromolecular flux in the small intestine.
Kimm
M H
MH
Gastrointestinal Research Group, University of Calgary, Alberta, Canada.
Hardin
J A
JA
Gall
D G
DG
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001692:Biological Transport; D015536:Down-Regulation; D007583:Jejunum / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D051381:Rats
D000418:Albumins; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester