Tonic regulation of mouse ileal ion transport by nitric oxide

Radhakrishna Rao, P. J M Riviere, X. Pascaud, J. L. Junien, F. Porreca

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The possible role of nitric oxide (NO) in the regulation of intestinal ion transport was studied in isolated sheets of mouse ileum mounted in Ussing flux chambers. The competitive NO-synthase inhibitors N(G)-methyl-L-arginine (L-NMA), and N(G)-nitro-L-arginine (L-NNA) and the effects of NO released from acidified sodium nitrite solution were evaluated in tissues pretreated with guanethidine and atropine. Serosal L-NMA or L-NNA (10-300 μM), but not N(G)-methyl-D-arginine (D-NMA), produced a sustained concentration-related increase in short-circuit current (I(sc)) and potential difference (PD) with maximal I(sc) increases of 50.8 ± 8.2 and 45.5 ± 5.8 μAmps/cm2, respectively; mucosal application of L-NMA or L-NNA produced transient increases in I(sc). The A50 (and 95% CL) values for serosal L-NMA and L- NNA were 25.6 (15.7-41.9) and 8.7 (5.1-14.9) μM, respectively. L-Arginine (0.1-10 mM), but not D-arginine, produced both a concentration-related reversal of L-NMA or L-NNA-induced increases in I(sc). Additionally, pretreatment with L-arginine blocked the L-NMA or L-NNA effects, suggesting a competitive interaction. L-NMA-mediated increases in I(sc) were unaffected by bicarbonate-free buffer, whereas replacement of chloride ions with gluconate ions almost completely attenuated the response to L-NMA. Further, the effects of L-NMA or L-NNA were blocked by tetrodotoxin or chlorisondamine, suggesting neural actions involving ganglionic transmission. Serosal application of acidified sodium nitrite solution (0.03-1.0 mM) produced a concentration- dependent and transient (3-6 min) decrease in I(sc) and PD, with an A50 (95% CL) value of 47 (36-62) μM. This sodium nitrite effect on ileal I(sc) was blocked by the pretreatment of tissue with hemoglobin (100 nM), which is known to trap free NO avidly, or methylene blue (5 μM), an inhibitor of soluble guanylate cyclase. Pretreatment with superoxide dismutase (25 U/ml), which prevents metabolism of NO by superoxide anion, prolonged the activity of sodium nitrite (0.3mM) from 5.3 ± 0.2 to 9.4 ± 0.7 min. These results suggest that NO produces a net proabsorptive effect on ion transport in mouse ileum, and that release of NO from nonadrenergic, noncholinergic nerves is involved in the tonic regulation of basal ion transport in this tissue.

Original languageEnglish (US)
Pages (from-to)626-631
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume269
Issue number2
StatePublished - 1994
Externally publishedYes

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Ion Transport
Sodium Nitrite
Arginine
Nitric Oxide
Ileum
Chlorisondamine
Ions
Guanethidine
Methylene Blue
Tetrodotoxin
Bicarbonates
Atropine
Nitric Oxide Synthase
Superoxides
Superoxide Dismutase
Chlorides
Buffers
Hemoglobins

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Rao, R., Riviere, P. J. M., Pascaud, X., Junien, J. L., & Porreca, F. (1994). Tonic regulation of mouse ileal ion transport by nitric oxide. Journal of Pharmacology and Experimental Therapeutics, 269(2), 626-631.

Tonic regulation of mouse ileal ion transport by nitric oxide. / Rao, Radhakrishna; Riviere, P. J M; Pascaud, X.; Junien, J. L.; Porreca, F.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 269, No. 2, 1994, p. 626-631.

Research output: Contribution to journalArticle

Rao, R, Riviere, PJM, Pascaud, X, Junien, JL & Porreca, F 1994, 'Tonic regulation of mouse ileal ion transport by nitric oxide', Journal of Pharmacology and Experimental Therapeutics, vol. 269, no. 2, pp. 626-631.
Rao, Radhakrishna ; Riviere, P. J M ; Pascaud, X. ; Junien, J. L. ; Porreca, F. / Tonic regulation of mouse ileal ion transport by nitric oxide. In: Journal of Pharmacology and Experimental Therapeutics. 1994 ; Vol. 269, No. 2. pp. 626-631.
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N2 - The possible role of nitric oxide (NO) in the regulation of intestinal ion transport was studied in isolated sheets of mouse ileum mounted in Ussing flux chambers. The competitive NO-synthase inhibitors N(G)-methyl-L-arginine (L-NMA), and N(G)-nitro-L-arginine (L-NNA) and the effects of NO released from acidified sodium nitrite solution were evaluated in tissues pretreated with guanethidine and atropine. Serosal L-NMA or L-NNA (10-300 μM), but not N(G)-methyl-D-arginine (D-NMA), produced a sustained concentration-related increase in short-circuit current (I(sc)) and potential difference (PD) with maximal I(sc) increases of 50.8 ± 8.2 and 45.5 ± 5.8 μAmps/cm2, respectively; mucosal application of L-NMA or L-NNA produced transient increases in I(sc). The A50 (and 95% CL) values for serosal L-NMA and L- NNA were 25.6 (15.7-41.9) and 8.7 (5.1-14.9) μM, respectively. L-Arginine (0.1-10 mM), but not D-arginine, produced both a concentration-related reversal of L-NMA or L-NNA-induced increases in I(sc). Additionally, pretreatment with L-arginine blocked the L-NMA or L-NNA effects, suggesting a competitive interaction. L-NMA-mediated increases in I(sc) were unaffected by bicarbonate-free buffer, whereas replacement of chloride ions with gluconate ions almost completely attenuated the response to L-NMA. Further, the effects of L-NMA or L-NNA were blocked by tetrodotoxin or chlorisondamine, suggesting neural actions involving ganglionic transmission. Serosal application of acidified sodium nitrite solution (0.03-1.0 mM) produced a concentration- dependent and transient (3-6 min) decrease in I(sc) and PD, with an A50 (95% CL) value of 47 (36-62) μM. This sodium nitrite effect on ileal I(sc) was blocked by the pretreatment of tissue with hemoglobin (100 nM), which is known to trap free NO avidly, or methylene blue (5 μM), an inhibitor of soluble guanylate cyclase. Pretreatment with superoxide dismutase (25 U/ml), which prevents metabolism of NO by superoxide anion, prolonged the activity of sodium nitrite (0.3mM) from 5.3 ± 0.2 to 9.4 ± 0.7 min. These results suggest that NO produces a net proabsorptive effect on ion transport in mouse ileum, and that release of NO from nonadrenergic, noncholinergic nerves is involved in the tonic regulation of basal ion transport in this tissue.

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