P(2) Purinoceptors Account for the Non-nitrergic NANC Relaxation in the Rat Ileum

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 2006 May 25

PMID 16721556

Citations 3

Authors

Rita Benko

Sarolta Undi

Matyas Wolf

Klara Magyar

Zsuzsanna Tovolgyi

Zoltan Rumbus

Lorand Bartho

Affiliations

Soon will be listed here.

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 P(2) purinoceptor antagonist for studying this response. We found that the P(2) purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 5x10(-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 alpha,beta-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 N(G)-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

Tanovic A, Jimenez M, Fernandez E . Actions of NO donors and endogenous nitrergic transmitter on the longitudinal muscle of rat ileum in vitro: mechanisms involved. Life Sci. 2001; 69(10):1143-54. DOI: 10.1016/s0024-3205(01)01198-5. View

Belai A, Burnstock G . 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. 1994; 278(1):197-200. DOI: 10.1007/BF00305792. View

Ziganshin A, Ziganshina L, King B, Pintor J, Burnstock G . Effects of P2-purinoceptor antagonists on degradation of adenine nucleotides by ecto-nucleotidases in folliculated oocytes of Xenopus laevis. Biochem Pharmacol. 1996; 51(7):897-901. DOI: 10.1016/0006-2952(95)02252-x. View

Ekblad E, Sundler F . 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. 1997; 283(1):23-8. View

Allescher H, Sattler D, Piller C, Schusdziarra V, Classen M . Ascending neural pathways in the rat ileum in vitro--effect of capsaicin and involvement of nitric oxide. Eur J Pharmacol. 1992; 217(2-3):153-62. DOI: 10.1016/0014-2999(92)90839-v. View

Kishi M, Takeuchi T, Suthamnatpong N, Ishii T, Nishio H, Hata F . 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. 1996; 119(4):623-30. PMC: 1915760. DOI: 10.1111/j.1476-5381.1996.tb15719.x. View

Rand M, Li C . Nitric oxide as a neurotransmitter in peripheral nerves: nature of transmitter and mechanism of transmission. Annu Rev Physiol. 1995; 57:659-82. DOI: 10.1146/annurev.ph.57.030195.003303. View

Costa M, Furness J, Humphreys C . Apamin distinguishes two types of relaxation mediated by enteric nerves in the guinea-pig gastrointestinal tract. Naunyn Schmiedebergs Arch Pharmacol. 1986; 332(1):79-88. DOI: 10.1007/BF00633202. View

Martins S, de Oliveira R, Ballejo G . Rat duodenum nitrergic-induced relaxations are cGMP-independent and apamin-sensitive. Eur J Pharmacol. 1995; 284(3):265-70. DOI: 10.1016/0014-2999(95)00348-o. View

10.

Yagasaki O, Nabata H, YANAGIYA I . Effects of desensitization to adenosine 5'-triphosphate and vasoactive intestinal polypeptide on non-adrenergic inhibitory responses of longitudinal and circular muscles in the rat ileum. J Pharm Pharmacol. 1983; 35(12):818-20. DOI: 10.1111/j.2042-7158.1983.tb02904.x. View

11.

Bennett M . Non-adrenergic non-cholinergic (NANC) transmission to smooth muscle: 35 years on. Prog Neurobiol. 1997; 52(3):159-95. DOI: 10.1016/s0301-0082(97)00012-9. View

12.

Paton W, Vizi E . The inhibitory action of noradrenaline and adrenaline on acetylcholine output by guinea-pig ileum longitudinal muscle strip. Br J Pharmacol. 1969; 35(1):10-28. PMC: 1703074. DOI: 10.1111/j.1476-5381.1969.tb07964.x. View

13.

Kaputlu I, Sadan G . Evidence that nitric oxide mediates non-adrenergic non-cholinergic relaxation induced by GABA and electrical stimulation in the rat isolated duodenum. J Auton Pharmacol. 1996; 16(4):177-82. DOI: 10.1111/j.1474-8673.1996.tb00420.x. View

14.

Serio R, Mule F, Adamo E, Postorino A . Evidence against purines being neurotransmitters of non-adrenergic, non-cholinergic nerves in rat duodenum. Eur J Pharmacol. 1990; 182(3):487-95. DOI: 10.1016/0014-2999(90)90046-9. View

15.

Bartho L, Koczan G, Petho G, Maggi C . Blockade of nitric oxide synthase inhibits nerve-mediated contraction in the rat small intestine. Neurosci Lett. 1992; 145(1):43-6. DOI: 10.1016/0304-3940(92)90199-h. View

16.

Niioka S, Takeuchi T, Kishi M, Ishii T, Nishio H, Takewaki T . Nonadrenergic, noncholinergic relaxation in longitudinal muscle of rat jejunum. Jpn J Pharmacol. 1997; 73(2):155-61. DOI: 10.1254/jjp.73.155. View

17.

Zagorodnyuk V, Santicioli P, Maggi C, Giachetti A . The possible role of ATP and PACAP as mediators of apaminsensitive NANC inhibitory junction potentials in circular muscle of guinea-pig colon. Br J Pharmacol. 1996; 119(5):779-86. PMC: 1915952. DOI: 10.1111/j.1476-5381.1996.tb15740.x. View

18.

Kanada A, Hata F, Suthamnatpong N, Maehara T, Ishii T, Takeuchi T . Key roles of nitric oxide and cyclic GMP in nonadrenergic and noncholinergic inhibition in rat ileum. Eur J Pharmacol. 1992; 216(2):287-92. DOI: 10.1016/0014-2999(92)90372-b. View

19.

Postorino A, Serio R, Mule F . Nitric oxide is involved in non-adrenergic, non-cholinergic inhibitory neurotransmission in rat duodenum. J Auton Pharmacol. 1995; 15(2):65-71. DOI: 10.1111/j.1474-8673.1995.tb00292.x. View

20.

Lambrecht G, Friebe T, Grimm U, Windscheif U, Bungardt E, Hildebrandt C . PPADS, a novel functionally selective antagonist of P2 purinoceptor-mediated responses. Eur J Pharmacol. 1992; 217(2-3):217-9. DOI: 10.1016/0014-2999(92)90877-7. View