Claudin-19 mediates the effects of NO on the paracellular pathway in thick ascending limbs
| Autor: | Jeffrey L. Garvin, Casandra Margarita Monzón |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Charge selectivity Physiology 030232 urology & nephrology Nitric Oxide Second Messenger Systems digestive system Membrane Potentials Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Chlorides Dibutyryl Cyclic GMP Loop of Henle medicine Animals Nitric Oxide Donors Claudin Cyclic GMP Tight junction urogenital system Chemistry Sodium Renal Reabsorption Perfusion 030104 developmental biology medicine.anatomical_structure Paracellular transport Claudins Biophysics Spermine tissues Research Article |
| Zdroj: | Am J Physiol Renal Physiol |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.00065.2019 |
| Popis: | Claudins are a family of tight junction proteins that provide size and charge selectivity to solutes traversing the paracellular space. Thick ascending limbs (TALs) express numerous claudins, including claudin-19. Nitric oxide (NO), via cGMP, reduces dilution potentials in perfused TALs, a measure of paracellular permeability, but the role of claudin-19 is unknown. We hypothesized that claudin-19 mediates the effects of NO/cGMP on the paracellular pathway in TALs via increases in plasma membrane expression of this protein. We measured the effect of the NO donor spermine NONOate (SPM) on dilution potentials with and without blocking antibodies and plasma membrane expression of claudin-19. During the control period, the dilution potential was −18.2 ± 1.8 mV. After treatment with 200 μmol/l SPM, it was −14.7 ± 2.0 mV ( P < 0.04). In the presence of claudin-19 antibody, the dilution potential was −12.7 ± 2.1 mV. After SPM, it was −12.9 ± 2.4 mV, not significantly different. Claudin-19 antibody alone had no effect on dilution potentials. In the presence of Tamm-Horsfall protein antibody, SPM reduced the dilution potential from −9.7 ± 1.0 to −6.3 ± 1.1 mV ( P < 0.006). Dibutyryl-cGMP (500 µmol/l) reduced the dilution potential from −19.6 ± 2.6 to −17.2 ± 2.3 mV ( P < 0.002). Dibutyryl-cGMP increased expression of claudin-19 in the plasma membrane from 29.9 ± 3.8% to 65.9 ± 10.1% of total ( P < 0.011) but did not change total expression. We conclude that claudin-19 mediates the effects of the NO/cGMP signaling cascade on the paracellular pathway. |
| Databáze: | OpenAIRE |
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