Nitric oxide modulates neuropeptide Y regulation of ion transport in mouse ileum

R. K. Rao, Y. Lopez, P. J.M. Riviere, X. Pascaud, J. L. Junien, F. Porreca

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Abstract

The possible involvement of nitric oxide in the regulation of intestinal ion transport induced by neuropeptide Y (NPY) was investigated by evaluating the effects of N(G)-methyl-L-arginine (L-NMA), L-arginine and S-nitroso-N - acetylpenicillamine (SNAP) on NPY activity in mouse ileum mounted in Ussing chambers in vitro. Serosal NPY (10 nM) produced a sustained decrease in basal transmural short circuit current (I(sc)) and potential difference without altering the tissue conductance. Pretreatment of tissues with L-arginine (3 mM), but not o-arginine (10 mM), blocked the NPY-mediated changes in I(sc). This L-arginine effect on NPY activity was reversed by L-NMA (3 mM), and not by N(G)-methyl-D-arginine (10 mM). The L-arginine effect on NPY activity was concentration-related with an A50 (95% CL) value of 1.6 (0.9-2.3) mM. In contrast to L-arginine, L-NMA (1 mM) pretreatment of tissues produced an enhancement of NPY activity, resulting in a 3.8-fold leftward displacement of the NPY concentration-response curve; N(G)-methyl-D-arginine was with out effect. The effect of L-NMA on NPY activity was concentration-related with an A50 (95% CL) value of 45.3 (23.2-68.8) μM. Serosal application of SNAP, a nitric oxide donor, produced a concentration-related decrease in basal I(sc) and potential difference without altering tissue conductance with an A50 (95% CL) value of 22.5 (11.1-40.5) μM. Pretreatment of tissue with SNAP (100 μM) reduced the NPY activity with rightward displacement of NPY concentration-response curve. Pretreatment of tissues with L-arginine also blocked the reduction of I(sc) by [D-Pen2,D-Pen5]enkephalin (10-30 nM), H2N-Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2 (10-30 nM) and somatostatin (0.3-1.0 μM), but had no effect on norepinephrine (0.1-0.3 μM)-induced decrease in mouse ileal I(sc). These results show that [fgc]I-arginine and SNAP block NPY-mediated changes in ion transport, suggesting that nitric oxide may play a role in the regulation of NPY-mediated ion transport in the mouse ileum.

Original languageEnglish (US)
Pages (from-to)193-198
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume278
Issue number1
StatePublished - Jul 1 1996

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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