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
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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
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↵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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