Summary
The role of nitric oxide (NO) in 5-HT-induced non-adrenergic non-cholinergic (NANC) relaxations was studied on circular muscle strips of the canine ileocolonic junction (ICJ) and terminal ileum. During an acetylcholine-induced contraction, NO (10−5 M) evoked a transient relaxation, whereas 5-HT (10−4 M) caused an initial NANC relaxation followed by a contraction. This initial relaxation to 5-HT, but not the relaxation to NO, was significantly inhibited by the stereospecific inhibitors of the NO biosynthesis NG-monomethyl-Larginine (L-NMMA) and NG-nitro-Irarginine (L-NNA). Larginine, but not D-arginine, prevented the inhibitory effect of L-NMMA and LNNA. The enantiomer of L-NMMA, D-NMMA, had no effect. Hemoglobin abolished the NO-induced relaxations and significantly inhibited the relaxation to 5-HT.
From these experiments it is concluded that the 5-HT-induced NANC relaxation is mediated by NO or a NO releasing substance.
Similar content being viewed by others
References
Boeckxstaens GE, Pelckmans PA, Bult H, De Man JG, Herman AG, Van Maercke YM (1990a) Non-adrenergic non-cholinergic relaxation mediated by nitric oxide in the canine ileocolonic junction. Eur J Pharmacol 190:239–246
Boeckxstaens GE, Pelckmans PA, Rampart M, Bogers JJ, Verbeuren TJ, Herman AG, Van Maercke YM (1990b) Pharmacological characterization of 5-hydroxytryptamine receptors in the canine terminal ileum and ileocolonic junction. J Pharmacol Exp Ther 254:652–658
Boeckxstaens GE, Pelckmans PA, Bogers JJ, Bult H, De Man JG, Oosterbosch L, Herman AG, Van Maercke YM (1991a) Release of nitric oxide upon stimulation of non-adrenergic non-cholinergic nerves in the rat gastric fundus. J Pharmacol Exp Ther 256:441–447
Boeckxstaens GE, Pelckmans PA, Ruytjens IF, Bult H, De Man JG, Herman AG, Van Maercke YM (1991b) Bioassay of nitric oxide released upon stimulation of non-adrenergic non-cholinergic nerves in the canine ileocolonic junction. Br J Pharmacol 103:1085–1091
Boeckxstaens GE, Pelckmans PA, Bult H, De Man JG, Herman AG, Van Maercke YM (1991c) Evidence for nitric oxide as mediator of non-adrenergic non-cholinergic relaxations induced by ATP and GABA in the canine gut. Br J Pharmacol 102:434–438
Bult H, Boeckxstaens GE, Pelckmans PA, Jordaens FH, Van Maercke YM, Herman AG (1990) Nitric oxide as a possible inhibitory non-adrenergic non-cholinergic neurotransmitter. Nature 345:346–347
Cassuto J, Jodal M, Sjovall H, Lundgren O (1981) Nervous control of intestinal secretion. Clin Res Rev 1 [Suppl]:12–16
Costall B, Naylor RJ (1990) 5-Hydroxytryptamine: New receptors and novel drugs for gastrointestinal motor disorders. Scand J Gastroenterol 25:769–787
De Man JG, Pelckmans PA, Boeckxstaens GE, Bult H, Oosterbosch L, Herman AG, Van Maercke YM (1991) The role of nitric oxide in inhibitory non-adrenergic, non-cholinergic neurotransmission in the canine lower esophageal sphincter. Br J Pharmacol 103:1092–1096
Garthwaite J, Charles SL, Chess-Williams R (1988) Endothelium-derived relaxing factor release on activation of NMDA receptors suggests role as intercellular messenger in the brain. Nature 336:385–388
Gibson A, Mirzazadeh S, Hobbs AJ, Moore PK (1990) L-NG-monomethyl arginine and L-NG -nitro arginine inhibit non-adrenergic, non-cholinergic relaxation of the mouse anococcygeus muscle. Br J Pharmacol 99:602–606
Gillespie JS (1990) Nonpurine, nonpeptide mechanisms. Arch Int Pharmacodyn 303:20–29
Kelm M, Feelish M, Spahr R, Piper H-M, Noack E, Schrader J (1988) Quantitative and kinetic characterization of nitric oxide and EDRF released from cultured endothelial cells. Biochem Biophys Res Commun 154:236–244
Knowles RG, Palacios M, Palmer RMJ, Moncada S (1989) Formation of nitric oxide from Larginine in the central nervous system: A transduction mechanism for stimulation of soluble guanylate cyclase. Proc Natl Acad Sci USA 86:5159–5162
Palmer RMJ, Ferrige AG, Moncada S (1987) Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327:524–526
Palmer RMJ, Rees DD, Ashton DS, Moncada S (1988) L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem Biophys Res Commun 153:1251–1256
Pelckmans PA, Boeckxstaens GE, Van Maercke YM, Herman AG, Verbeuren TJ (1989) Acetylcholine is an indirect inhibitory transmitter in the canine ileocolonic junction. Eur J Pharmacol 170:235–242
Talley NJ, Phillips SF, Haddad A, Miller LJ, Twomey C, Zinsmeister AR, Ciociola A (1989) Effect of selective 5HT3 antagonist (GR 38032F) on small intestinal transit and release of gastrointestinal peptides. Dig Dis Sci 34:1511–1515
Viner CV, Selby PJ, Zulian GB, Gore ME, Butcher ME, Wootton CM, McElwain TJ (1990) Ondansetron — a new safe and effective antiemetic in patients receiving high dose melphalan. Cancer Chemother Pharmacol 25:449–453
Author information
Authors and Affiliations
Additional information
Research Assistant of the National Fund for Scientific Research Belgium (NFWO)
Send offprint requests to Y.M. Van Maercke at the above address
Rights and permissions
About this article
Cite this article
Bogers, J.J., Pelckmans, P.A., Boeckxstaens, G.E. et al. The role of nitric oxide in serotonin-induced relaxations in the canine terminal ileum and ileocolonic junction. Naunyn-Schmiedeberg's Arch Pharmacol 344, 716–719 (1991). https://doi.org/10.1007/BF00174756
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00174756