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OtherGASTROINTESTINAL PHARMACOLOGY

l-Arginine Deficiency Causes Suppression of Nonadrenergic Noncholinergic Nerve-Mediated Smooth Muscle Relaxation: Role of l-Citrulline Recycling

Sushanta Chakder and Satish Rattan
Journal of Pharmacology and Experimental Therapeutics July 1997, 282 (1) 378-384;
Sushanta Chakder
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Satish Rattan
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Abstract

Studies were performed on the internal anal sphincter (IAS) smooth muscle strips obtained from opossums (Didelphis virginiana). Isometric tension and l-arginine levels of the tissues were measured under basal conditions, in the presence of electrical field stimulation (EFS) and after treatment with different concentrations of arginase. For the nonadrenergic noncholinergic nerve stimulation, short trains (4 sec) as well as continuous EFS were used. During continuous EFS, after the initial IAS relaxation, the response began to fade within several min to ∼80% recovery of the basal tone. We also examined the influence ofl-arginine and l-citrulline on these responses. For some studies, the tissues were pretreated withl-glutamine (an inhibitor of l-citrulline uptake), l-glutamate or NG-hydroxy-l-arginine (an inhibitor of arginase). Interestingly, the basal levels of l-arginine were found to be significantly higher in the IAS (tonic smooth muscle) than in the rectal (phasic smooth muscle) smooth muscle. Arginase caused a concentration-dependent attenuation of the IAS relaxation caused by EFS. l-Citrulline and l-arginine were equipotent in reversing the attenuation. Both arginase (60 min pretreatment) and continuous EFS (tissues collected at the time of maximal recovery of the basal IAS tone after the initial relaxation) caused significant decreases in l-arginine levels. The decreases in the levels of l-arginine were restored by the exogenous administration of either l-arginine orl-citrulline. The restoration of l-arginine levels by l-citrulline but not by l-arginine was selectively blocked by l-glutamine. Furthermore, the IAS relaxation, attenuated by arginase was unaffected byl-glutamine but was restored by NG-hydroxy-l-arginine pretreatment. The studies suggest that l-citrulline-l-arginine recycling may play a significant role in the maintenance of IAS relaxation in response to nonadrenergic noncholinergic nerve stimulation.

Footnotes

  • Send reprint requests to: Dr. Satish Rattan, Professor of Medicine and Physiology, 901 College, Department of Medicine, Division of Gastroenterology & Hepatology, 1025 Walnut Street, Philadelphia, PA 19107.

  • ↵1 The work was supported by United States Public Health Service Grant DK-35385 from the National Institutes of Health and an institutional grant from Thomas Jefferson University.

  • Abbreviations:
    IAS
    internal anal sphincter
    EFS
    electrical field stimulation
    NANC
    nonadrenergic noncholinergic
    NO
    nitric oxide
    NOS
    nitric oxide synthase
    HOArg
    NG-hydroxy-l-arginine
    • Received October 16, 1996.
    • Accepted March 10, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 282, Issue 1
1 Jul 1997
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OtherGASTROINTESTINAL PHARMACOLOGY

l-Arginine Deficiency Causes Suppression of Nonadrenergic Noncholinergic Nerve-Mediated Smooth Muscle Relaxation: Role of l-Citrulline Recycling

Sushanta Chakder and Satish Rattan
Journal of Pharmacology and Experimental Therapeutics July 1, 1997, 282 (1) 378-384;

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OtherGASTROINTESTINAL PHARMACOLOGY

l-Arginine Deficiency Causes Suppression of Nonadrenergic Noncholinergic Nerve-Mediated Smooth Muscle Relaxation: Role of l-Citrulline Recycling

Sushanta Chakder and Satish Rattan
Journal of Pharmacology and Experimental Therapeutics July 1, 1997, 282 (1) 378-384;
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