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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Influence of Heme Oxygenase Inhibitors on the Basal Tissue Enzymatic Activity and Smooth Muscle Relaxation of Internal Anal Sphincter

Satish Rattan and Sushanta Chakder
Journal of Pharmacology and Experimental Therapeutics September 2000, 294 (3) 1009-1016;
Satish Rattan
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Sushanta Chakder
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Abstract

We examined the actions of different heme oxygenase (HO) inhibitors on the basal HO activity in the opossum internal anal sphincter (IAS), rectum, and liver tissues and the IAS smooth muscle relaxation in response to nonadrenergic noncholinergic (NANC) nerve stimulation and different agonists. All the tissues examined were found to have significant levels of basal HO activity. Among different HO inhibitors, tin protoporphyrin IX (SnPP IX) was found to be most selective in inhibiting the HO activity in the IAS smooth muscle. Conversely, in the liver, all the HO inhibitors except SnPP IX caused significant inhibition of HO activity. Consistent with HO activity inhibition, the IAS smooth muscle relaxations caused by NANC nerve stimulation and vasoactive intestinal polypeptide also were inhibited by zinc protoporphyrin IX and SnPP IX. Zinc protoporphyrin IX also caused a significant attenuation of the IAS smooth muscle relaxation caused by isoproterenol. The IAS smooth muscle relaxation caused by nitric oxide was not significantly modified by any of the HO inhibitors. The data show the presence of HO activity in the IAS and other gastrointestinal tissues. The differential attenuation of HO activity by different HO inhibitors in the IAS smooth muscle and liver confirms the presence of different isozymes of HO in different tissues. Suppression of basal HO activity and the IAS smooth muscle relaxation induced by NANC nerve stimulation or VIP but not NO suggest that some of the stimuli that cause IAS smooth muscle relaxation may involve HO activity.

Footnotes

  • Send reprint requests to: Dr. Satish Rattan, Professor of Medicine and Physiology, Jefferson Medical College, Thomas Jefferson University, 1025 Walnut St., Room 901 College, Philadelphia, PA 19107. E-mail: Satish.Rattan{at}mail.tju.edu

  • ↵1 The study was supported by National Institutes of Diabetes and Digestive and Kidney Diseases Grant DK-35385 and an institutional grant from Thomas Jefferson University.

  • Abbreviations:
    CO
    carbon monoxide
    LES
    lower esophageal sphincter
    IAS
    internal anal sphincter
    HO
    heme oxygenase
    ZnPP IX
    zinc protoporphyrin IX
    NANC
    nonadrenergic noncholinergic
    VIP
    vasoactive intestinal polypeptide
    AC
    adenylate cyclase
    NO
    nitric oxide
    GC
    guanylate cyclase
    EFS
    electrical field stimulation
    ZnDP IX
    zinc deuteroporphyrin IX
    SnPP IX
    tin protoporphyrin IX
    CuPP III
    coproporphyrin III
    ICC
    interstitial cells of Cajal
    • Received January 18, 2000.
    • Accepted May 16, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 294 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 294, Issue 3
1 Sep 2000
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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Influence of Heme Oxygenase Inhibitors on the Basal Tissue Enzymatic Activity and Smooth Muscle Relaxation of Internal Anal Sphincter

Satish Rattan and Sushanta Chakder
Journal of Pharmacology and Experimental Therapeutics September 1, 2000, 294 (3) 1009-1016;

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Research ArticleGASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Influence of Heme Oxygenase Inhibitors on the Basal Tissue Enzymatic Activity and Smooth Muscle Relaxation of Internal Anal Sphincter

Satish Rattan and Sushanta Chakder
Journal of Pharmacology and Experimental Therapeutics September 1, 2000, 294 (3) 1009-1016;
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