The effect of the selective PAF antagonist CIS-19 on PAF- and antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity in guinea-pigs |
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| Authors: | Chien-Huang Lin Feng-Nien Ko Hisahi Ishii Tsutomu Ishikawa Ih-Sheng Chen Che-Ming Teng H-P Kuo |
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| Institution: | (1) Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan, TW;(2) Faculty of Pharmaceutical Sciences, Chiba University, Chiba, Japan, JP;(3) School of Pharmacy, Kaohsiung Medical College, Kaohsiung, Taiwan, TW;(4) Department of Thoracic Medicine, Chang Gung Memorial Hospital, No.199, Tun-Hwa North Road, Taipei, Taiwan, TW |
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| 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 bronchial hyperreactivity. These results suggest that PAF plays
little or no role in early airway responses following antigen challenge.
Received: 29 April 1996 / Accepted: 10 October 1996 |
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| Keywords: | PAF receptor antagonist Bronchoconstriction Microvascular leakage Bronchial hyperreactivity Antigen challenge Guinea-pigs |
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