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P2 purinoceptors account for the non-nitrergic NANC relaxation in the rat ileum

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Abstract

The transmitters involved in the non-nitrergic component of the non-adrenergic, non-cholinergic (NANC) inhibitory response of the rat small intestinal longitudinal muscle to electrical field stimulation of its nerves is a matter of controversy. The present study is the first one to utilise a combination of a nitric oxide synthase inhibitor and a P2 purinoceptor antagonist for studying this response. We found that the P2 purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS; 5×10−5 M) abolished the non-nitrergic NANC relaxation to electrical field stimulation (10 Hz). PPADS alone provided a significant, moderate inhibitory action. PPADS specifically inhibited relaxations due to exogenous adenosine 5′-triphosphate (ATP) or α,β-methylene ATP. The guanylate cyclase blocker 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10−6 M) did not add to the inhibitory action of NG-nitro-L-arginine on field stimulation-induced relaxation. ODQ abolished the relaxant effect of the nitric oxide donors nitroglycerin or sodium nitroprusside. These data indicate that: (1) nitric oxide and ATP fully account for the field stimulation-induced relaxation in the rat ileal strip under the experimental conditions of this study, and (2) no ODQ-sensitive guanylate cyclase-mediated mechanism is involved in the non-nitrergic component of the NANC relaxation.

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References

  • Allescher H-D, Sattler D, Piller C, Schusdziarra V, Classen M (1992) Ascending neural pathways in the rat ileum in in vitro - effect of capsaicin and involvement of nitric oxide. Eur J Pharmacol 217:153–162

    Article  PubMed  CAS  Google Scholar 

  • Barthó L, Lefebvre RA (1995) Nitric oxide-mediated contraction in enteric smooth muscle. Arch Int Pharmacodyn Ther 329:53–66

    PubMed  Google Scholar 

  • Barthó L, Kóczán G, Pethö G, Maggi CA (1992) Blockade of nitric oxide synthase inhibits nerve-mediated contraction in the rat small intestine. Neurosci Lett 145:43–46

    Article  PubMed  Google Scholar 

  • Belai A, Burnstock G (1994) Evidence for coexistence of ATP and nitric oxide in non-adrenergic, non-cholinergic (NANC) inhibitory neurones in the rat ileum, colon and anococcygeus muscle. Cell Tissue Res 278:197–200

    Article  PubMed  CAS  Google Scholar 

  • Bennett MR (1997) Non-adrenergic non-cholinergic (NANC) transmission to smooth muscle: 35 years on. Prog Neurobiol 52:159–195

    Article  PubMed  CAS  Google Scholar 

  • Costa M, Furness JB, Humphreys CMS (1986) Apamin distinguishes two types of relaxation mediated by enteric nerves in the guinea-pig gastrointestinal tract. Naunyn-Schmiedeberg’s Arch Pharmacol 332:79–88

    Article  PubMed  CAS  Google Scholar 

  • Ekblad E, Sundler F (1997) Motor responses in rat ileum evoked by nitric oxide donors vs. field stimulation: modulation by pituitary adenylate cyclase-activating peptide, forskolin and guanylate cyclase inhibitors. J Pharmacol Exp Ther 283:23–28

    PubMed  CAS  Google Scholar 

  • Ferrero JD, Cocks T, Burnstock G (1980) A comparison between ATP and bradykinin as possible mediators of the responses of smooth muscle to non-adrenergic non-cholinergic nerves. Eur J Pharmacol 63:295–302

    Article  PubMed  CAS  Google Scholar 

  • Kanada A, Hata F, Suthamnatpong N, Maehara T, Ishii T, Takeuchi T, Yagasaki O (1992) Key roles of nitric oxide and cyclic GMP in nonadrenergic and noncholinergic inhibition in rat ileum. Eur J Pharmacol 216:287–292

    Article  PubMed  CAS  Google Scholar 

  • Kaputlu I, Sadan G (1997) Evidence that nitric oxide mediates non-adrenergic non-cholinergic relaxation induced by GABA and electrical stimulation in the rat isolated duodenum. J Auton Pharmacol 16:177–182

    Article  Google Scholar 

  • Kishi M, Takeuchi T, Suthamnatpong N, Ishii T, Nishio H, Hata F, Takewaki T (1996) VIP- and PACAP-mediated nonadrenergic, noncholinergic inhibition in longitudinal muscle of rat distal colon: involvement of activation of charybdotoxin- and apamin-sensitive K+ channels. Br J Pharmacol 119:623–630

    PubMed  CAS  Google Scholar 

  • Lambrecht G, Friebe T, Grimm U, Windscheif U, Bungardt E, Hildebrandt C, Bäumert HG, Spatz-Kümbel G, Mutschler E (1992) PPADS, a novel functionally selective antagonist of P2-purinoceptor mediated responses. Eur J Pharmacol 217:217–219

    Article  PubMed  CAS  Google Scholar 

  • Manzini S, Maggi CA, Meli A (1986) Pharmacological evidence that at least two different non-adrenergic non-cholinergic inhibitory systems are present in the rat small intestine. Eur J Pharmacol 123:229–236

    Article  PubMed  CAS  Google Scholar 

  • Martins SL, De Oliveira RB, Ballejo G (1995) Rat duodenum nitrergic-induced relaxations are cGMP-independent and apamin-sensitive. Eur J Pharmacol 284:265–270

    Article  PubMed  CAS  Google Scholar 

  • Niioka S, Takeuchi T, Kishi M, Ishii T, Nishio H, Takewaki T, Hata F (1997) Nonadrenergic, noncholinergic relaxation in longitudinal muscle of rat jejunum. Jpn J Pharmacol 73:155–161

    Article  PubMed  CAS  Google Scholar 

  • Paton WDM, Vizi ES (1969) The inhibitory action of noradrenaline and adrenaline on acetylcholine output by guinea-pig ileum longitudinal muscle strip. Br J Pharmacol 35:10–20

    PubMed  CAS  Google Scholar 

  • Postorino A, Serio R, Mulè F (1995) Nitric oxide is involved in non-adrenergic, non-cholinergic inhibitory neurotransmission in rat duodenum. J Auton Pharmacol 15:65–71

    Article  PubMed  CAS  Google Scholar 

  • Rand MJ, Li CG (1995) Nitric oxide as a neurotransmitter in peripheral nerves: nature of transmitter and mechanism of transmission. Ann Rev Physiol 57:659–682

    Article  CAS  Google Scholar 

  • Serio R, Mule F, Adamo EB, Postorino A (1990) Evidence against purines being neurotransmitters of non-adrenergic, non-cholinergic nerves in rat duodenum. Eur J Pharmacol 182:487–495

    Article  PubMed  CAS  Google Scholar 

  • Smits GJM, Lefebvre RA (1996) ATP and nitric oxide: inhibitory NANC neurotransmitters in the longitudinal muscle-myenteric plexus preparation of the rat ileum. Br J Pharmacol 118:695–703

    PubMed  CAS  Google Scholar 

  • Tanovic A, Jimenez M, Fernandez E (2001) Actions of NO donors and endogenous nitrergic transmitter on the longitudinal muscle of rat ileum in vitro: mechanisms involved. Life Sci 69:1143–1154

    Article  PubMed  CAS  Google Scholar 

  • Yagasaki O, Nabata H, Yanagiya I (1983) Effects of desensitization to adenosine 5′-triphosphate and vasoactive intestinal polypeptide on non-adrenergic inhibitory response of longitudinal and circular muscles in the rat ileum. J Pharm Pharmacol 35:818–820

    PubMed  CAS  Google Scholar 

  • Yamaji M, Ohta M, Yamazaki Y, Fujinami K, Fujita A, Takeuchi T, Hata F, Takewaki T (2002) A possible role of neurotensin in NANC relaxation of longitudinal muscle of the jejunum and ileum of Wistar rats. Br J Pharmacol 137:629–636

    Article  PubMed  CAS  Google Scholar 

  • Zagorodnyuk V, Santicioli P, Maggi CA, Giachetti A (1996) The possible role of ATP and PACAP as mediators of apamin-sensitive NANC inhibitory junction potentials in circular muscle of guinea-pig colon. Br J Pharmacol 119:779–786

    PubMed  CAS  Google Scholar 

  • Ziganshin AU, Ziganshina LE, King BF, Pintor J, Burnstock G (1996) Effects of P2-purinoceptor antagonists on degradation of adenine nucleotides by ecto-nucleotidases in folliculated oocytes of Xenopus laevis. Biochem Pharmacol 51:897–901

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by the Hungarian Research Funds (OTKA, grants No. T-031895, T-046770, T-037523, TS-040753, M-036322); Ministries of Welfare (ETT-04-185/2003, ETT-03-326/2003) and Education (PhD fellowship for S.U.).

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Authors and Affiliations

  1. Department of Pharmacology and Pharmacotherapy, Division of Pharmacodynamics, University Medical School of Pécs, Szigeti u. 12, H-7643, Pécs, Hungary

    Rita Benkó, Sarolta Undi, Matyas Wolf, Klara Magyar, Zsuzsanna Tóvölgyi, Zoltan Rumbus & Lorand Barthó

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  1. Rita Benkó
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  2. Sarolta Undi
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  3. Matyas Wolf
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  4. Klara Magyar
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  6. Zoltan Rumbus
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  7. Lorand Barthó
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Correspondence to Lorand Barthó.

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Benkó, R., Undi, S., Wolf, M. et al. P2 purinoceptors account for the non-nitrergic NANC relaxation in the rat ileum. Naunyn-Schmied Arch Pharmacol 373, 319–324 (2006). https://doi.org/10.1007/s00210-006-0070-5

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  • DOI: https://doi.org/10.1007/s00210-006-0070-5

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