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Tetrahydrobiopterin Regulates Cyclic GMP‐Dependent Electrogenic Cl − Secretion in Mouse Ileum In Vitro
Author(s) -
Rolfe V. E.,
Brand M. P.,
Heales S. J. R.,
Lindley K. J.,
Milla P. J.
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1997.347bh.x
Subject(s) - ileum , nitric oxide , chemistry , carbachol , tetrahydrobiopterin , medicine , nitrite , endocrinology , cyclic guanosine monophosphate , guanosine , arginine , nitric oxide synthase , biochemistry , biology , stimulation , amino acid , organic chemistry , nitrate
1 Basal electrogenic Cl − secretion, measured as the short‐circuit current ( I sc ), was variable in ileum removed from tetrahydrobiopterin (BH 4 )‐deficient hph ‐1 mice and wild‐type controls in vitro , although values were not significantly different. 2 The basal nitrite release and mucosal cyclic guanosine 3′,5′‐monophosphate (cyclic GMP) production were similar in control and BH 4 ‐deficient ileum. 3 Mucosally added Escherichia coli heat‐stable toxin (STa, 55 ng ml −1 ) increased the nitrite release, cyclic GMP levels and the I sc in control ileum, but its secretory actions were reduced in BH 4 ‐deficient ileum. 4 L‐Arginine (1 mM) increased the nitrite release, cyclic GMP production and the I sc in control ileum, but the actions were reduced in BH 4 ‐deficient ileum. 5 Serosal carbachol (1 mM) stimulated maximum short‐circuit currents of similar magnitude in both control and BH 4 ‐deficient ileum, whilst nitrite release and cyclic GMP production were minimal. 6 E. 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 BH 4 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.