Role of carbon monoxide in electrically induced non-adrenergic, non-cholinergic relaxations in the guinea-pig isolated whole trachea

A. Dellabianca, M. Sacchi, L. Anselmi, E. De Amici, E. Cervio, A. Agazzi, S. Tonini, C. Sternini, M. Tonini, S. M. Candura

Research output: Contribution to journalArticlepeer-review

Abstract

Background and purpose:Nitric oxide (NO) and vasoactive intestinal peptide (VIP) are considered transmitters of non-adrenergic, non-cholinergic (NANC) relaxations in guinea-pig trachea, whereas the role of carbon monoxide (CO) is unknown. This study was designed to assess the participation of CO, and to investigate the localization of haem oxygenase-2 (HO-2), the CO-producing enzyme, in tracheal neurons.Experimental approach:NANC responses to electrical field stimulation (EFS) at 3 and 10 Hz were evaluated in epithelium-free whole tracheal segments as intraluminal pressure changes. Drugs used were: L-nitroarginine methyl ester (L-NAME, 100 μM) to inhibit NO synthase (NOS), α-chymotrypsin (2 U ml -1) to inactivate VIP, zinc protoporphyrin-IX (ZnPP-IX, 10 μM) to inhibit HO-2, and 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 μM), a soluble guanylyl cyclase inhibitor. For immunohistochemistry, tissues were exposed to antibodies to PGP 9.5, a general neuronal marker, HO-2 and NOS, and processed with an indirect immunofluorescence method.Key results:α-Chymotrypsin did not affect NANC relaxations. ODQ inhibited NANC responses by about 60%, a value similar to that obtained by combining L-NAME and ZnPP-IX. The combination of ODQ, L-NAME and ZnPP-IX reduced the responses by 90%. Subpopulations of HO-2 positive neurons containing NOS were detected in tracheal sections.Conclusions and Implications:In the guinea-pig trachea, NANC inhibitory responses at 3 and 10 Hz use NO and CO as main transmitters. Their participation is revealed following inhibition of NOS, HO-2 and soluble guanylyl cyclase. The involvement of CO as a relaxing transmitter paves the way for novel therapeutic approaches in the treatment of airway obstruction.

Original languageEnglish
Pages (from-to)220-226
Number of pages7
JournalBritish Journal of Pharmacology
Volume150
Issue number2
DOIs
Publication statusPublished - Jan 2007

Keywords

  • Carbon monoxide
  • Electrical field stimulation
  • Guinea-pig
  • Immunohistochemistry
  • NANC inhibitory innervation
  • Nitric oxide
  • Trachea
  • Vasoactive intestinal peptide

ASJC Scopus subject areas

  • Pharmacology

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