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OtherGASTROINTESTINAL PHARMACOLOGY

Inhibitory Effect of Zinc Protoporphyrin IX on Lower Esophageal Sphincter Smooth Muscle Relaxation by Vasoactive Intestinal Polypeptide and Other Receptor Agonists

Ya-Ping Fan, Sushanta Chakder and Satish Rattan
Journal of Pharmacology and Experimental Therapeutics May 1998, 285 (2) 468-474;
Ya-Ping Fan
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Sushanta Chakder
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Satish Rattan
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Abstract

This study was performed in the opossum lower esophageal sphincter (LES) smooth muscle strips to determine the action of the heme oxygenase inhibitor zinc protoporphyrin IX (ZnPP IX) on the relaxant effect of vasoactive intestinal polypeptide and isoproterenol, which are known to stimulate adenylate cyclase (AC) via G protein coupling, and of the direct activator of AC catalytic subunit forskolin. To investigate the cGMP pathway, we examined the effect of atrial natriuretic factor known to activate the receptor linked to the particulate guanylate cyclase via G protein coupling and that of sodium nitroprusside [nitric oxide (NO) donor], authentic NO and carbon monoxide, which stimulate the intracellular soluble fraction of GC. The smooth muscle relaxation caused by nonadrenergic noncholinergic (NANC) nerve stimulation also was investigated. ZnPP IX caused concentration-dependent attenuation of the relaxant effect of vasoactive intestinal polypeptide, isoproterenol and atrial natriuretic factor without any effect on that of forskolin, sodium nitroprusside, NO and CO. Interestingly, ZnPP IX had no significant effect on the LES relaxation caused by NANC nerve stimulation and the smooth muscle contraction by bethanechol. From these results, we conclude that ZnPP IX attenuates the LES smooth muscle relaxation caused by the stimulation of G protein-coupled receptors to particulate AC and guanylate cyclase. The lack of effect of ZnPP IX on the NANC nerve-mediated LES relaxation suggests either lack of a role of heme oxygenase pathway in the response or an up-regulation of NOS leading to normal LES relaxation.

Footnotes

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

  • ↵1 This work was supported by National Institutes of Diabetes and Digestive and Kidney Diseases Grant DK35385 and an institutional grant from Thomas Jefferson University.

  • Abbreviations:
    LES
    lower esophageal sphincter
    IAS
    internal anal sphincter
    ZnPP IX
    zinc protoporphyrin IX
    SnPP IX
    tin protoporphyrin IX
    EFS
    electrical field stimulation
    NANC
    nonadrenergic noncholinergic
    HO
    heme oxygenase
    NOS
    nitric oxide synthase
    L-NA
    NG-nitro-l-arginine
    VIP
    vasoactive intestinal polypeptide
    PHI
    peptide histidine isoleucine
    AC
    adenylate cyclase
    cAMP
    cyclic AMP
    ANF
    atrial natriuretic factor
    SNP
    sodium nitroprusside
    GC
    guanylate cyclase
    cGMP
    cyclic GMP
    • Received August 12, 1997.
    • Accepted January 21, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 285, Issue 2
1 May 1998
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OtherGASTROINTESTINAL PHARMACOLOGY

Inhibitory Effect of Zinc Protoporphyrin IX on Lower Esophageal Sphincter Smooth Muscle Relaxation by Vasoactive Intestinal Polypeptide and Other Receptor Agonists

Ya-Ping Fan, Sushanta Chakder and Satish Rattan
Journal of Pharmacology and Experimental Therapeutics May 1, 1998, 285 (2) 468-474;

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Inhibitory Effect of Zinc Protoporphyrin IX on Lower Esophageal Sphincter Smooth Muscle Relaxation by Vasoactive Intestinal Polypeptide and Other Receptor Agonists

Ya-Ping Fan, Sushanta Chakder and Satish Rattan
Journal of Pharmacology and Experimental Therapeutics May 1, 1998, 285 (2) 468-474;
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