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Substance P antagonist does not block the stimulation of rapidly adapting pulmonary stretch receptors by ammonia

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Abstract

We investigated the effects of the substance P (SP) blocker [D-Pro2,D-Trp7,9]-SP on the response of rapidly adapting pulmonary stretch receptors (RARs) to SP administered into the right atrium, or ammonia vapor inhaled into the lungs in anesthetized, spontaneously breathing rabbits. Right atrial administration of SP (0.3, 1.0, and 3.0 µg/kg) caused an increase in the RAR activity, and this increase became more prominent as the dose of SP was increased. The RARs increased their activity following inhalation of vapor from 5 and 10% ammonia solutions, and the increase was concentration dependent. The excitatory responses of RAR activity to SP at different doses were greatly diminished or completely blocked by administration of the selective SP antagonist (300 and 500 µg/kg). However, the ammonia-induced RAR stimulation was not significantly altered by prior treatment with the SP blocker (300 and 500 µg/kg). These results suggest that the stimulation of RARs by ammonia does not occur as a result of the release of SP from sensory nerves in the airways and lungs.

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References

  1. Andersson P, Persson H (1977) Effects of substance P on pulmonary resistance and dynamic pulmonary compliance in the anesthetized cat and guinea pig. Acta Pharmacol Toxicol 41:444–448

    Google Scholar 

  2. Armstrong DJ, Luck JG (1974) A comparative study on irritant and type J receptors in the cat. Respir Physiol 21:47–60

    Google Scholar 

  3. Bergren DR, Sampson SR (1982) Characterization of intra-pulmonary rapidly adapting receptors of guinea pig. Respir Physiol 47:83–95

    Google Scholar 

  4. Das RM, Jeffery PK, Widdicombe JG (1979) Experimental degeneration of intra-epitherial nerve fibers in cat airways. J Anat 128:259–267

    Google Scholar 

  5. Grandordy BM, Frossard N, Rhoden KJ, Barnes PJ (1988) Tachykinin-induced phosphoinositide breakdown in airway smooth muscle and epithelium: relation to contraction. Mol Pharmacol 33:515–519

    Google Scholar 

  6. Holzer P (1991) Capsaicin: cellular targets, mechanisms of action, and selectivity for sensory neurons. Pharmacol Rev 43:143–201

    Google Scholar 

  7. Hua H-Y, Theodorsson-Norheim E, Brodin E, Lundberg JM, Hokfelt T (1985) Multiple tachykinins (neurokinin A, neuropeptide K, and substance P) in capsaicin-sensitive sensory neurons in the guinea-pig. Regul Pept 13:1–19

    Google Scholar 

  8. Jonzon A, Pisarri TE, Coleridge JCG, Coleridge HM (1986) Rapidly adpating receptor activity in dogs is inversely related to lung compliance. J Appl Physiol 61:1980–1986

    Google Scholar 

  9. Kappagoda CT, Ravi K (19890) Plasmaphresis affects responses of slowly and rapidly adapting airway receptors to pulmonary venous congestion in dogs. J Physiol (Lond) 416:79–91

    Google Scholar 

  10. Kappagoda CT, Man GCW, Teo KK (1987) Behaviour of canine pulmonary vagal afferent receptors during sustained acute pulmonary venous pressure elevation. J Physiol (Lond) 394:249–265

    Google Scholar 

  11. Kappagota CT, Man GCW, Ravi K, Teo KK (1988) Reflex tracheal contraction during pulmonary venous congestion in the dog. J Physiol (Lond) 402:335–346

    Google Scholar 

  12. Karlsson J-A, Finney MJB, Persson CGA, Post C (1984) Substance P antagonists and the role of tachykinins in noncholinergic bronchoconstriction. Life Sci 35:2681–2691

    Google Scholar 

  13. Laitinen LA, Laitinen A, Panula PA, Partnen M, Tervo K, Tervo T (1983) Immunohistochemical demonstration of substance P in the lower respiratory tract of the rabbit and not of man. Thorax 38:531–536

    Google Scholar 

  14. Lundberg LM, Saria A (1982) Capsaicin-sensitive vagal neurons involved in control of vascular permeability in rat trachea. Acta Physiol Scand 115:521–523

    Google Scholar 

  15. Lundberg LM, Saria A (1982) Bronchial smooth muscle contration induced by stimulation of capsaicin-sensitive vagal sensory neurons. Acta Physiol Scand 116:473–476

    Google Scholar 

  16. Lundberg LM, Saria A (1983) Capsaicin-induced desensitization of airway mucosa to cigarette smoke, mechanical, and chemical irritants. Nature 302:251–253

    Google Scholar 

  17. Lundberg LM, Saria A, Brodin E, Rosel S, Folkers KA (1983) Substance P antagonist inhibits vagally induced increase in vascular permeability and bronchial smooth muscle contraction in the guinea pig. Proc Natl Acad Sci 80:1120–1124

    Google Scholar 

  18. Lundberg LM, Brodin E, Saria A (1983) Effects and distribution of vagal capsaicin-sensitive substance P neurons with special reference to the trachea and lungs. Acta Physiol Scand 119:243–252

    Google Scholar 

  19. Lundberg JM, Hokfelt T, Martling C-R, Saria A, Cuello C (1984) Sensory substance P-immunoreactive nerves in the lower respiratory tract of various mammals including man. Cell Tissue Res 235:251–261.

    Google Scholar 

  20. Maggi CA (1991) The pharmacology of the efferent function of sensory nerves. J Ant Pharmac 11:173–208

    Google Scholar 

  21. Martling C-R, Theodorsson-Norheim E, Norheim I, Lundberg JM (1987) Bronchoconstrictor and hypotensive effects in relation to pharmacokinetic tachykinins in the guinea-pig—evidence for extraneuronal cleavage of neuropeptide K to neurokinin A. Naunyn-Schmiedeberg's Arch Pharmacol 336:183–189

    Google Scholar 

  22. Matsumoto S (1989) Effects of ammonia and histamine on lung irritant receptors in the rabbit. Respir Physiol 77:301–308

    Google Scholar 

  23. Matsumoto S, Kanno T, Yamasaki M, Nagayama T, Shimizu T (1992) Pulmonary c-fibers elicit both apneusis and tachypnea in the rabbit. Respir Physiol 87:165–181

    Google Scholar 

  24. Matsumoto S, Kanno T, Yamasaki M, Nagayama T, Shimizu T H1- and H2-receptor influences of histamine and ammonia on rapidly adapting pulmonary stretch receptor activities. J Auton Nerv Syst 43: 17–26

  25. Mills JE, Sellick H, Widdicombe JG (1969) Activity of lung irritant receptors in pulmonary microembolism, anaphylaxis, and drug-induced bronchoconstriction. J Physiol (Lond) 203:337–357

    Google Scholar 

  26. Palmer JBD, Barnes PJ (1987) Neuropeptides and airway smooth muscle function. Am Rev Respir Dis 136:S50-S54

    Google Scholar 

  27. Pisarri TE, Jonzon A, Coleridge JCG, Coleridge HM (1990) Rapidly adapting receptors monitor lung compliance in spontaneously breathing dogs. J Appl Physiol 68:1997–2005

    Google Scholar 

  28. Saria A, Martling C-R, Yan Z, Theodorsson-Norheim E, Gamse R, Lundberg JM (1988) Release of multiple tachykinins from capsaicin-sensitive sensory nerves in the lung by bradykinin, histamine, dimethylphenylpiperazinium, and vagal stimulation. Am Rev Respir Dis 137:1330–1335

    Google Scholar 

  29. Tanaka DT, Grunstein MM (1984) Mechanisms of substance P-induced contraction of rabbit airway smooth muscle. J Appl Physiol 57:1551–1557

    Google Scholar 

  30. Tanaka DT, Grunstein MM (1986) Effect of substance P on neurally mediated contraction of rabbit airway smooth muscle. J Appl Physiol 60:458–463

    Google Scholar 

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Authors and Affiliations

  1. Department of Physiology, Fukushima Medical College, 1 Hikari-gaoka, Fukushima City, 960-12, Fukushima, Japan

    S. Matsumoto, M. Yamasaki, T. Kanno, T. Nagayama, M. Tanno & T. Shimizu

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  1. S. Matsumoto
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  2. M. Yamasaki
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  3. T. Kanno
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  4. T. Nagayama
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  5. M. Tanno
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  6. T. Shimizu
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Matsumoto, S., Yamasaki, M., Kanno, T. et al. Substance P antagonist does not block the stimulation of rapidly adapting pulmonary stretch receptors by ammonia. Lung 172, 31–45 (1994). https://doi.org/10.1007/BF00186167

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