Tetrahydrobiopterin Regulates Cyclic GMP-Dependent Electrogenic Cl− Secretion in Mouse Ileum In Vitro
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V. E. Rolfe: email@example.com
- 1Basal electrogenic Cl− secretion, measured as the short-circuit current (Isc), was variable in ileum removed from tetrahydrobiopterin (BH4)-deficient hph-1 mice and wild-type controls in vitro, although values were not significantly different.
- 2The basal nitrite release and mucosal cyclic guanosine 3′,5′-monophosphate (cyclic GMP) production were similar in control and BH4-deficient ileum.
- 3Mucosally added Escherichia coli heat-stable toxin (STa, 55 ng ml−1) increased the nitrite release, cyclic GMP levels and the Isc in control ileum, but its secretory actions were reduced in BH4-deficient ileum.
- 4L-Arginine (1 mM) increased the nitrite release, cyclic GMP production and the Isc in control ileum, but the actions were reduced in BH4-deficient ileum.
- 5Serosal carbachol (1 mM) stimulated maximum short-circuit currents of similar magnitude in both control and BH4-deficient ileum, whilst nitrite release and cyclic GMP production were minimal.
- 6E. coli STa and L-arginine increased electrogenic Cl− secretion across intact mouse ileum in vitro by releasing nitric oxide and elevating mucosal cyclic GMP. The inhibition of these processes in the hph-1 mouse ileum suggests that BH4 may be a target for the modulation of electrogenic transport, and highlight the complexity of the interactions between nitric oxide and cyclic GMP in the gut.