The effect of the selective PAF antagonist CIS-19 on PAF- and antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity in guinea-pigs

Chien-Huang Lin, Feng Nien Ko, Hisahi Ishii, Tsutomu Ishikawa, Ih Sheng Chen, Che Ming Teng, Han Pin Kuo

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

We investigated the effects of a novel platelet-activating factor (PAF) receptor antagonist, CIS-19 [cis-2-(3, 4-dimethoxyphenyl)-6-isopropoxy-7-methoxy-1-(N- methylformamido)-1, 2, 3, 4-tetrahydronaphthalene], on PAF-, histamine-, substance P- and antigen-induced bronchoconstriction and microvascular leakage, as well as PAF- and antigen induced bronchial hyperreactivity to methacholine in urethane-anesthetized guinea-pigs. Administration of CIS-19 (0.5-5 mg/kg, i.v.) inhibited the increase in lung resistance induced by PAF (30 ng/kg, i.v.) in a dose-dependent manner, but failed to inhibit the increase induced by histamine (30 μg/kg, i.v.) or substance P (6.5 μg/kg, i.v. CIS-19 (5 mg/kg, i.v.) did not inhibit the increase in lung resistance induced by ovalbumin (2 mg/kg, i.v.) in actively sensitized guinea-pigs. PAF (30 ng/kg, i.v.)-induced microvascular leakage, measured by the extravasation of Evans blue dye, was dose-dependently inhibited by CIS-19 (0.5-5 mg/kg, i.v.) in the trachea, main bronchi and intrapulmonary airways, but it did not affect histamine (30 μg/kg, i.v.)- or substance P (6.5 μg/kg, i.v.)-induced microvascular leakage at all airway levels. CIS-19 (2.5 and 5 mg/kg) did not affect ovalbumin (2 mg/kg, i.v.)-induced microvascular leakage in all airway levels in actively sensitized guinea-pigs. CIS-19 (2.5 and 5 mg/kg, i.v.) significantly inhibited PAF-induced enhancement of the bronchial response to methacholine, but had no effect on ovalbumin (0.05 mg/kg, i.v.)-induced bronchial hyperreactivity in actively sensitized guinea-pigs. It is concluded that CIS-19 is a potent PAF receptor antagonist which inhibits PAF- but not antigen-induced bronchoconstriction, microvascular leakage and bronchialhyperreactivity. These results suggest that PAF plays little or no role in early airway responses following antigen challenge.

Original languageEnglish
Pages (from-to)210-216
Number of pages7
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume355
Issue number2
DOIs
Publication statusPublished - 1997
Externally publishedYes

Fingerprint

Bronchial Hyperreactivity
Bronchoconstriction
Platelet Activating Factor
Guinea Pigs
Antigens
Ovalbumin
Substance P
Histamine
Methacholine Chloride
Lung
Evans Blue
CIS 19
Urethane
Bronchi
Trachea
Coloring Agents

Keywords

  • Antigen challenge
  • Bronchial hyperreactivity
  • Bronchoconstriction
  • Guinea-pigs
  • Microvascular leakage
  • PAF receptor antagonist

ASJC Scopus subject areas

  • Pharmacology

Cite this

The effect of the selective PAF antagonist CIS-19 on PAF- and antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity in guinea-pigs. / Lin, Chien-Huang; Ko, Feng Nien; Ishii, Hisahi; Ishikawa, Tsutomu; Chen, Ih Sheng; Teng, Che Ming; Kuo, Han Pin.

In: Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 355, No. 2, 1997, p. 210-216.

Research output: Contribution to journalArticle

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