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. 1995 May;115(1):158–162. doi: 10.1111/j.1476-5381.1995.tb16333.x

Pharmacological identification of different inhibitory mediators involved in the innervation of the internal anal sphincter.

A Tøttrup 1, M A Knudsen 1, F Hanberg Sørensen 1, E B Glavind 1
PMCID: PMC1908751  PMID: 7647971

Abstract

1. Inhibitory non-adrenergic, non-cholinergic (NANC) responses were studied in isolated strips from the rabbit internal anal sphincter. 2. In the presence of atropine and guanethidine, transmural field stimulation induced frequency-dependent relaxations that reached a plateau at frequencies > or = 4 Hz. 3. These relaxations were inhibited by apamin (10(-6) M) and by N omega-nitro-L-arginine (L-NOARG, 10(-4) M). With these two substances in combination, relaxations were still seen in response to field stimulation, but only at frequencies > 2 Hz. 4. In the presence of both apamin (10(-6) M) and L-NOARG (10(-4) M), responses at high frequencies consisted of a fast relaxation followed by a slow return to prestimulus tension level. alpha-Chrymotrypsin hastens the return of tension to prestimulus level after high frequency stimulation. 5. Zinc-protoporphyrin IX, an inhibitor of haeme oxygenase, had a significant inhibitory effect on relaxations induced by transmural field stimulation. It was found, however, that responses to sodium nitroprusside and to isoprenaline (both 10(-9)-10(-4) M) were reduced comparably, indicating that the effect of zinc-protoporphyrin IX was unspecific. 6. It is concluded that pharmacological analysis allows identification of at least three distinguishable components of the inhibitory NANC innervation of the rabbit internal anal sphincter. The study does not allow conclusions about the role of carbon monoxide, a recently proposed mediator of NANC responses in opossum internal anal sphincter.

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Selected References

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  1. Banks B. E., Brown C., Burgess G. M., Burnstock G., Claret M., Cocks T. M., Jenkinson D. H. Apamin blocks certain neurotransmitter-induced increases in potassium permeability. Nature. 1979 Nov 22;282(5737):415–417. doi: 10.1038/282415a0. [DOI] [PubMed] [Google Scholar]
  2. Bult H., Boeckxstaens G. E., Pelckmans P. A., Jordaens F. H., Van Maercke Y. M., Herman A. G. Nitric oxide as an inhibitory non-adrenergic non-cholinergic neurotransmitter. Nature. 1990 May 24;345(6273):346–347. doi: 10.1038/345346a0. [DOI] [PubMed] [Google Scholar]
  3. Costa M., Furness J. B., Humphreys C. M. Apamin distinguishes two types of relaxation mediated by enteric nerves in the guinea-pig gastrointestinal tract. Naunyn Schmiedebergs Arch Pharmacol. 1986 Jan;332(1):79–88. doi: 10.1007/BF00633202. [DOI] [PubMed] [Google Scholar]
  4. Gillespie J. S., Liu X. R., Martin W. The effects of L-arginine and NG-monomethyl L-arginine on the response of the rat anococcygeus muscle to NANC nerve stimulation. Br J Pharmacol. 1989 Dec;98(4):1080–1082. doi: 10.1111/j.1476-5381.1989.tb12650.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Jury J., Jager L. P., Daniel E. E. Unusual potassium channels mediate nonadrenergic noncholinergic nerve-mediated inhibition in opossum esophagus. Can J Physiol Pharmacol. 1985 Feb;63(2):107–112. doi: 10.1139/y85-020. [DOI] [PubMed] [Google Scholar]
  6. Knudsen M. A., Tøttrup A. A possible role of the L-arginine-nitric oxide pathway in the modulation of cholinergic transmission in the guinea-pig taenia coli. Br J Pharmacol. 1992 Nov;107(3):837–841. doi: 10.1111/j.1476-5381.1992.tb14533.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Li C. G., Rand M. J. Evidence for a role of nitric oxide in the neurotransmitter system mediating relaxation of the rat anococcygeus muscle. Clin Exp Pharmacol Physiol. 1989 Dec;16(12):933–938. doi: 10.1111/j.1440-1681.1989.tb02404.x. [DOI] [PubMed] [Google Scholar]
  8. Lim S. P., Muir T. C. Neuroeffector transmission in the guinea-pig internal anal sphincter: an electrical and mechanical study. Eur J Pharmacol. 1986 Aug 22;128(1-2):17–24. doi: 10.1016/0014-2999(86)90552-2. [DOI] [PubMed] [Google Scholar]
  9. Maas A. J., Den Hertog A. The effect of apamin on the smooth muscle cells of the guinea-pig taenia coli. Eur J Pharmacol. 1979 Sep 15;58(2):151–156. doi: 10.1016/0014-2999(79)90006-2. [DOI] [PubMed] [Google Scholar]
  10. Maas A. J. The effects of apamin on responses evoked by field stimulation in guinea-pig taenia caeci. Eur J Pharmacol. 1981 Jul 17;73(1):1–9. doi: 10.1016/0014-2999(81)90139-4. [DOI] [PubMed] [Google Scholar]
  11. Maines M. D. Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications. FASEB J. 1988 Jul;2(10):2557–2568. [PubMed] [Google Scholar]
  12. Maines M. D. Zinc . protoporphyrin is a selective inhibitor of heme oxygenase activity in the neonatal rat. Biochim Biophys Acta. 1981 Mar 18;673(3):339–350. doi: 10.1016/0304-4165(81)90465-7. [DOI] [PubMed] [Google Scholar]
  13. Moore P. K., al-Swayeh O. A., Chong N. W., Evans R. A., Gibson A. L-NG-nitro arginine (L-NOARG), a novel, L-arginine-reversible inhibitor of endothelium-dependent vasodilatation in vitro. Br J Pharmacol. 1990 Feb;99(2):408–412. doi: 10.1111/j.1476-5381.1990.tb14717.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. O'Kelly T., Brading A., Mortensen N. Nerve mediated relaxation of the human internal anal sphincter: the role of nitric oxide. Gut. 1993 May;34(5):689–693. doi: 10.1136/gut.34.5.689. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rattan S., Chakder S. Inhibitory effect of CO on internal anal sphincter: heme oxygenase inhibitor inhibits NANC relaxation. Am J Physiol. 1993 Oct;265(4 Pt 1):G799–G804. doi: 10.1152/ajpgi.1993.265.4.G799. [DOI] [PubMed] [Google Scholar]
  16. Rees D. D., Palmer R. M., Hodson H. F., Moncada S. A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent relaxation. Br J Pharmacol. 1989 Feb;96(2):418–424. doi: 10.1111/j.1476-5381.1989.tb11833.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Shuba M. F., Vladimirova I. A. Effect of apamin on the electrical responses of smooth muscle to adenosine 5'-triphosphate and to non-adrenergic, non-cholinergic nerve stimulation. Neuroscience. 1980;5(5):853–859. doi: 10.1016/0306-4522(80)90154-2. [DOI] [PubMed] [Google Scholar]
  18. Tøttrup A., Glavind E. B., Svane D. Involvement of the L-arginine-nitric oxide pathway in internal anal sphincter relaxation. Gastroenterology. 1992 Feb;102(2):409–415. doi: 10.1016/0016-5085(92)90084-c. [DOI] [PubMed] [Google Scholar]
  19. Tøttrup A., Svane D., Forman A. Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter. Am J Physiol. 1991 Mar;260(3 Pt 1):G385–G389. doi: 10.1152/ajpgi.1991.260.3.G385. [DOI] [PubMed] [Google Scholar]
  20. Verma A., Hirsch D. J., Glatt C. E., Ronnett G. V., Snyder S. H. Carbon monoxide: a putative neural messenger. Science. 1993 Jan 15;259(5093):381–384. doi: 10.1126/science.7678352. [DOI] [PubMed] [Google Scholar]

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