Nonadrenergic Noncholinergic Nerve-mediated Contraction of the Longitudinal Muscle of Rat Ileum

랫드 회장 종주근의 비아드레날린 비콜린성 신경에 의한 수축반응

  • Kim, Tae-wan (College of Veterinary Medicine, Biotechnology Research Institute, Chonnam National University) ;
  • La, Jun-ho (College of Veterinary Medicine, Seoul National University) ;
  • Sung, Tae-sik (College of Veterinary Medicine, Seoul National University) ;
  • Kang, Jung-woo (College of Veterinary Medicine, Seoul National University) ;
  • Yang, Il-suk (College of Veterinary Medicine, Seoul National University) ;
  • Han, Ho-jae (College of Veterinary Medicine, Biotechnology Research Institute, Chonnam National University)
  • 김태완 (전남대학교 수의과대학 생리학교실/생물공학연구소) ;
  • 나준호 (서울대학교 수의과대학 생리학교실) ;
  • 성태식 (서울대학교 수의과대학 생리학교실) ;
  • 강정우 (서울대학교 수의과대학 생리학교실) ;
  • 양일석 (서울대학교 수의과대학 생리학교실) ;
  • 한호재 (전남대학교 수의과대학 생리학교실/생물공학연구소)
  • Accepted : 2003.08.07
  • Published : 2003.09.25

Abstract

The purpose of this study was to assess the role of tachykinins (TK) in mediating nonadrenergic noncholinergic (NANC) contractions produced by electrical field stimulation (EFS) in the longitudinal muscle of the rat ileum. In the presence of atropine ($1{\mu}M$), guanethidine ($5{\mu}M$), and L-nitroarginine (L-NNA, $200{\mu}M$), EFS (0.5ms pulse duration, 120 V, 1-20 Hz for 2 min) produced a frequency-dependent slowly-developing tonic contraction with superimposed phasic contractions ('on'-contraction) followed by off slowly-decreasing tonic and superimposed phasic contractions ('off'-contraction) of mucosa-free longitudinal oriented muscle strip. These EFS induced responses were blocked by tetrotoxin. $NK_1$ receptor selective antagonist L-732,138 strongly inhibited the EFS-induced excitatory responses. However $NK_2$ receptor selective antagonist, GR 159897 and $NK_3$ receptor selective antagonist SB 222200 did not significantly inhibited the responses. $NK_1$ receptor selective agonist [$Sar^9$,$Met(O_2)^{11}$] Substance P and $NK_2$ receptor selective agonist [${\beta}-Ala^8$]-neurokinin A (4-10) induced tonic contraction with superimposed phasic contractions of longitudinal oriented muscle strip and almost blocked by selective antagonist L-732,138 and GR 159897, respectively. But $NK_3$ receptor selective agonist senktide did not showed any effect. Nifedipine ($1{\mu}M$) abolished the contraction produced either by EFS or by the TK receptor agonists [$Sar^9$,$Met(O_2)^{11}$] Substance P or [${\beta}-Ala^8$]-neurokinin A (4-10). It is concluded that, in the longitudinal muscle of rat ileum, both $NK_1$ and $NK_2$ receptors modulated the responses to exogenous tachykinins, whereas $NK_1$ is mainly involved in NANC neuromuscular contraction.

Acknowledgement

Supported by : Korea Research Foundation

References

  1. Beresford, I. J., Sheldrick, R. L., Ball, D. I., Turpin, M. P., Walsh, D. M., Hawcock, A. B., Coleman, R. A., Hagan, R. M. and Tyers, M. B. GR159897, a potent non-peptide antagonist at tachykinin NK2 receptois. Eur. J. Pharmacol. 1995, 272(2-3), 241-248
  2. Maggi, C. A., Giuliani, S. and Zagorodnyuk, V. Sequential activation of the triple excitatory trans- mission to the circular muscle of guinea-pig colon. Neurosci. 1997, 79(1), 263-274
  3. Mann, P. T., Southwell, B. R., Ding, Y. Q., Shigemoto, R., Mizuno, N. and Furness, J. B. Localisation of neurokinin 3 (NK3) receptor immuno- reactivity in the rat gastrointestinal tract. Cell Tissue Res. 1997, 289(1), 1-9
  4. Nguyen, L., Nguyen, Q. T., Gobeil, F., Jukic, D., Chretien, L. and Regoli, D. Neurokinin receptors in the guinea pig ileum. Pharmacol. 1996, 52(1), 35-45
  5. Onori, L., Aggio, A., Taddei, G., Ciccocioppo, R., Severi, C, Carnicelli, V. and Tonini, M Contribution of NK3 tachykinin receptors to propulsion in the rabbit isolated distal colon. Neurogastroenterol. Motil. 2001, 13(3), 211-219
  6. Severini, C., Improta, G., Falconieri-Erspamer, G., Salvadori, S. and Erspamer, V. The tachykinin peptide family. Pharmacol. Rev. 2002, 54(2), 285-322
  7. Smith, T. K. and Robertson. W. J. Synchronous movements of the longitudinal and circular muscle during peristalsis in the isolated guinea-pig distal colon. J. Physiol. 1998, 506(2), 563-577
  8. Willis, S., Allescher, H. D., Schusdziarra, V., Regoli, D., Drapeau, G. and Classen, M. Differential effects of selective neurokinin agonists on phasic and tonic activity in rat ileal longitudinal muscle. Neuropept. 1993, 25(5), 315-323
  9. Zagorodnyuk, V., Santicioli, P., Turini, D. and Maggi, C. A. Tachykinin NKl and NK2 receptors mediate non-adrenergic non-cholinergic excitatory neuromuscular transmission in the human ileum. Neuropept. 1997, 31(3), 265-271
  10. Tolessa, T., Lordal, M. and Hellstrom, P. M. Contractile responses of mt duodenum caused by transmural nerve stimulation: interaction between tachykininergic and cholinergic mechanisms. Acta Physiol. Scand. 1996, 158(2), 135-142
  11. Maggi, C. A. and Giuliani, S. Role of tachykinins as excitatory mediators of NANC contraction in the circular muscle of rat small intestine. J. Auton. Pharmacol. 1995, 15(5), 335-350
  12. Saban, R., Nguyen, N., Saban, M. R., Gerard, N. P. and Pasricha, P. J. Nerve-mediated motility of ileal segments isolated from NK(1) receptor knockout mice. Am J. Physiol 1999, 277(61), 1173-1179
  13. Al Saffar, A. and Hellstrom, P. M. Contractile responses to natural tachykinins and selective tachykinin analogs in normal and inflamed ileal and colonic muscle. Scand. J. Gastroenterol. 2001, 36(5), 485-493
  14. Hellstrom, P. M., Murthy, K. S., Grider, J. R. and Makhlouf, G. M. Coexistence of three tachykinin receptors coupled to Ca++ signaling pathways in intestinal muscle cells. J. Pharmacol. Exp. Ther. 1994, 270(1), 236-243
  15. Vilain, P., Emonds-Alt, X., Le Fur, G. and Breliere, J. C. Tachykinin-induced contractions of the guinea pig ileum longitudinal smooth muscle: tonic and phasic muscular activities. Can. J. Physiol. Pharmacol. 1997, 75(6), 587-590
  16. Cao, W., Pricolo, V. E., Zhang, L., Behar, J., Biancani, P. and Kirber, M. T. Gq-Linked NK(2) Receptors mediate neurally induced contraction of human sigmoid circular smooth muscle. Gastroenterol. 2000, 119(1), 51-61
  17. Kojima, S. and Shimo, Y. Calcitonin gene-related peptide (CGRP)-enhanced non-adrenergic non-cholinergic contraction of guinea-pig proximal colon. Br. J. Pharmacol. 1995, 115(7), 1290-1294
  18. Zagorodnyuk, V., Santicioli, P., Maggi, C. A. and Giachetti, A. Evidence that tachykinin NKl and NK2 receptors mediate non-adrenergic non-cholinergic excitation and contraction in the circular muscle of guinea-pig duodenum. Br. J. Pharmacol. 1995, 115(2), 237-246
  19. Grider, J. R. Reciprocal activity of longitudinal and circular muscle during intestinal peristaltic reflex. Am. J. Physiol Gastrointest. Liver Physiol. 2003, 284(5), 768-775
  20. Serio, R., Mule, F., Bonvissuto, F. and Postorino, A. Tachykinins mediate noncholinergic excitatory neural responses in the circular muscle of rat proximal colon. Can. J. Physiol Pharmacol. 1998, 76(6), 684-689
  21. Pedersen, K. E., Buckner, C. K., Meeker, S. N. and Undem, B. J. Pharmacological examination of the neurokinin-l receptor mediating relaxation of human intralobar pulmonary artery. J. Pharmacol. Exp. Ther. 2000, 292(1), 319-325
  22. Maggi, C. A., Zagorodnyuk, V. and Giuliani, S. Specialization of tachykinin NKl and NK2 receptors in producing fast and slow atropine-resistant neuro- transmission to the circular muscle of the guinea-pig colon. Neurosci. 1994, 63(4), 1137-1152
  23. Suzuki, N., Mizuno, K. and Gomi, Y. Neurogenic 'off' contractions are mediated by NK2-receptors in the circular muscle of guinea pig ileum. Jpn. J. Pharmacol. 1994, 64(3), 213-216
  24. Holzer, P. and Holzer-Petsche, U. Tachykinins in the gut. Part I. Expression, release and motor function. Pharmacol. Ther. 1997, 73(3), 173-217