Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 Sep;104(1):49–52. doi: 10.1111/j.1476-5381.1991.tb12383.x

Prostacyclin activates tachykinin release from capsaicin-sensitive afferents in guinea-pig bronchi through a ruthenium red-sensitive pathway.

C E Mapp 1, L M Fabbri 1, A Boniotti 1, C A Maggi 1
PMCID: PMC1908289  PMID: 1723916

Abstract

1. We have investigated the ability of prostacyclin (PGI2) to contract guinea-pig isolated bronchi and the possible involvement of capsaicin-sensitive primary afferents in the response to PGI2. 2. PGI2 (0.1-100 microM) produced concentration-dependent contractions of the guinea-pig isolated bronchi. In vitro capsaicin desensitization (10 microM for 30 min followed by washing) significantly reduced the PGI2-induced contraction at all concentrations tested. A capsaicin-resistant component of contraction (40-60% of the overall response) was also evident. 3. Ruthenium red (3 microM), an inorganic dye which acts as a selective functional antagonist of capsaicin, significantly decreased PGI2-induced contractions, without affecting the response to substance P, neurokinin A or acetylcholine. 4. MEN 10, 207, (Tyr5, D-Trp6,8,9, Arg10)-neurokinin A (4-10) (3 microM), a selective antagonist of NK2-tachykinin receptors, significantly decreased PGI2-induced contractions and neurokinin A-induced contractions, without affecting the response to acetylcholine. 5. The effect of ruthenium red and MEN 10,207 on the one hand, and that of ruthenium red and capsaicin on the other was non additive. 6. These results indicate that PGI2-induced contraction of the guinea-pig isolated bronchi involves two distinct mechanisms, one of which involves transmitter (tachykinins) release from peripheral endings of capsaicin-sensitive primary afferents. In as much as PGI2-activation of primary afferents is sensitive to ruthenium red, we suggest that PGI2 shares a common mechanism of tachykinin release with that activated by capsaicin.

Full text

PDF
49

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bunting S., Gryglewski R., Moncada S., Vane J. R. Arterial walls generate from prostaglandin endoperoxides a substance (prostaglandin X) which relaxes strips of mesenteric and coeliac ateries and inhibits platelet aggregation. Prostaglandins. 1976 Dec;12(6):897–913. doi: 10.1016/0090-6980(76)90125-8. [DOI] [PubMed] [Google Scholar]
  2. Choudry N. B., Fuller R. W., Pride N. B. Sensitivity of the human cough reflex: effect of inflammatory mediators prostaglandin E2, bradykinin, and histamine. Am Rev Respir Dis. 1989 Jul;140(1):137–141. doi: 10.1164/ajrccm/140.1.137. [DOI] [PubMed] [Google Scholar]
  3. Dray A., Forbes C. A., Burgess G. M. Ruthenium red blocks the capsaicin-induced increase in intracellular calcium and activation of membrane currents in sensory neurones as well as the activation of peripheral nociceptors in vitro. Neurosci Lett. 1990 Mar 2;110(1-2):52–59. doi: 10.1016/0304-3940(90)90786-9. [DOI] [PubMed] [Google Scholar]
  4. Lundberg J. M., Saria A., Brodin E., Rosell S., Folkers K. A substance P antagonist inhibits vagally induced increase in vascular permeability and bronchial smooth muscle contraction in the guinea pig. Proc Natl Acad Sci U S A. 1983 Feb;80(4):1120–1124. doi: 10.1073/pnas.80.4.1120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Maggi C. A. Capsaicin and primary afferent neurons: from basic science to human therapy? J Auton Nerv Syst. 1991 Apr;33(1):1–14. doi: 10.1016/0165-1838(91)90013-s. [DOI] [PubMed] [Google Scholar]
  6. Maggi C. A., Patacchini R., Baroldi P., Theodorsson E., Meli A. Immunoblockade by a specific tachykinin antiserum of the non-cholinergic contractile responses in the guinea-pig isolated bronchus. J Auton Pharmacol. 1990 Jun;10(3):173–179. doi: 10.1111/j.1474-8673.1990.tb00016.x. [DOI] [PubMed] [Google Scholar]
  7. Maggi C. A., Patacchini R., Giuliani S., Rovero P., Dion S., Regoli D., Giachetti A., Meli A. Competitive antagonists discriminate between NK2 tachykinin receptor subtypes. Br J Pharmacol. 1990 Jul;100(3):589–592. doi: 10.1111/j.1476-5381.1990.tb15851.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Maggi C. A., Patacchini R., Perretti F., Meini S., Manzini S., Santicioli P., Del Bianco E., Meli A. The effect of thiorphan and epithelium removal on contractions and tachykinin release produced by activation of capsaicin-sensitive afferents in the guinea-pig isolated bronchus. Naunyn Schmiedebergs Arch Pharmacol. 1990 Jan-Feb;341(1-2):74–79. doi: 10.1007/BF00195061. [DOI] [PubMed] [Google Scholar]
  9. Maggi C. A., Patacchini R., Santicioli P., Giuliani S., Del Bianco E., Geppetti P., Meli A. The 'efferent' function of capsaicin-sensitive nerves: ruthenium red discriminates between different mechanisms of activation. Eur J Pharmacol. 1989 Nov 7;170(3):167–177. doi: 10.1016/0014-2999(89)90537-2. [DOI] [PubMed] [Google Scholar]
  10. Mathé A. A., Hedqvist P. Effect of prostaglandins F2 alpha and E2 on airway conductance in healthy subjects and asthmatic patients. Am Rev Respir Dis. 1975 Mar;111(3):313–320. doi: 10.1164/arrd.1975.111.3.313. [DOI] [PubMed] [Google Scholar]
  11. Mathé A. A., Hedqvist P., Holmgren A., Svanborg N. Bronchial hyperreactivity to prostaglandin F 2 and histamine in patients with asthma. Br Med J. 1973 Jan 27;1(5847):193–196. doi: 10.1136/bmj.1.5847.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Roberts A. M., Bhattacharya J., Schultz H. D., Coleridge H. M., Coleridge J. C. Stimulation of pulmonary vagal afferent C-fibers by lung edema in dogs. Circ Res. 1986 Apr;58(4):512–522. doi: 10.1161/01.res.58.4.512. [DOI] [PubMed] [Google Scholar]
  13. Roberts A. M., Schultz H. D., Green J. F., Armstrong D. J., Kaufman M. P., Coleridge H. M., Coleridge J. C. Reflex tracheal contraction evoked in dogs by bronchodilator prostaglandins E2 and I2. J Appl Physiol (1985) 1985 Jun;58(6):1823–1831. doi: 10.1152/jappl.1985.58.6.1823. [DOI] [PubMed] [Google Scholar]
  14. Rovero P., Pestellini V., Maggi C. A., Patacchini R., Regoli D., Giachetti A. A highly selective NK-2 tachykinin receptor antagonist containing D-tryptophan. Eur J Pharmacol. 1990 Jan 3;175(1):113–115. doi: 10.1016/0014-2999(90)90161-x. [DOI] [PubMed] [Google Scholar]
  15. Smith A. P., Cuthbert M. F. The response of normal and asthmatic subjects to prostaglandins E2 and F2alpha by different routes, and their significance in asthma. Adv Prostaglandin Thromboxane Res. 1976;1:449–459. [PubMed] [Google Scholar]
  16. Szallasi A., Blumberg P. M. Specific binding of resiniferatoxin, an ultrapotent capsaicin analog, by dorsal root ganglion membranes. Brain Res. 1990 Jul 30;524(1):106–111. doi: 10.1016/0006-8993(90)90498-z. [DOI] [PubMed] [Google Scholar]
  17. Voelkel N. F., Gerber J. G., McMurtry I. F., Nies A. S., Reeves J. T. Release of vasodilator prostaglandin, PGI2, from isolated rat lung during vasoconstriction. Circ Res. 1981 Feb;48(2):207–213. doi: 10.1161/01.res.48.2.207. [DOI] [PubMed] [Google Scholar]
  18. Wasserman M. A., Ducharme D. W., Wendling M. G., Griffin R. L., Degraaf G. L. Bronchodilator effects of prostacyclin (PGI2) in dogs and guinea pigs. Eur J Pharmacol. 1980 Aug 22;66(1):53–63. doi: 10.1016/0014-2999(80)90294-0. [DOI] [PubMed] [Google Scholar]
  19. el-Kashef H. A., Hofman W. F., Ehrhart I. C. Prostacyclin production with serotonin, increased flow, or elevated venous pressure in dog lung. J Appl Physiol (1985) 1990 Oct;69(4):1283–1289. doi: 10.1152/jappl.1990.69.4.1283. [DOI] [PubMed] [Google Scholar]
  20. van Grondelle A., Worthen G. S., Ellis D., Mathias M. M., Murphy R. C., Strife R. J., Reeves J. T., Voelkel N. F. Altering hydrodynamic variables influences PGI2 production by isolated lungs and endothelial cells. J Appl Physiol Respir Environ Exerc Physiol. 1984 Aug;57(2):388–395. doi: 10.1152/jappl.1984.57.2.388. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES