PARTIAL INHIBITION BY EPITHELIUM OF TRACHEAL SMOOTH-MUSCLE RELAXATION INDUCED BY THE POTASSIUM CHANNEL ACTIVATOR, BRL-38227

被引：4

作者：

PAVLOVIC, D ^{[1
]}

BRIONE, E ^{[1
]}

DEVERNEJOUL, D ^{[1
]}

AUBIER, M ^{[1
]}

机构：

[1] FAC XAVIER BICHAT,INSERM,U226,PATHOL EXPTL LAB,PARIS,FRANCE

来源：

BRITISH JOURNAL OF PHARMACOLOGY | 1993年 / 110卷 / 01期

关键词：

SMOOTH MUSCLE; TRACHEAL EPITHELIUM; POTASSIUM CHANNEL ACTIVATOR; BRL-38227 (LEMAKALIM);

D O I：

10.1111/j.1476-5381.1993.tb13783.x

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

1 A method is described whereby either the serosal (Out) or epithelial (In) sides of rat isolated tracheae were selectively perfused. Perfusion with BRL 38227 (10(-8)-5 x 10(-6) m; In/Out) of preparations with intact epithelium (+ EP) precontracted with carbachol (10(-6) m; Out/In) produced complete relaxation. Perfusion with aminophylline (10(-5) - 10(-3) m; In) of + EP preparations precontracted with carbachol (10(-6) m; Out) also produced complete relaxation. 2 In preparations precontracted with carbachol (10(-6) m) epithelium removal (- EP) increased the sensitivity to the relaxant effect of BRL 38227 (In), but not BRL 38227 (Out) [- log EC50, + EP/ - EP; carbachol (In), BRL 38227 (Out): 6.76 +/- 0.11 vs 6.67 +/- 0.15; carbachol (Out), BRL 38227 (In): 5.93 +/- 0.06 vs 6.25 +/- 0.07]. Removal of the epithelium increased also the sensitivity to BRL 38227 (In) of preparations precontracted with a lower concentration (5 x 10(-7) M) of carbachol (Out). [- log EC50, + EP/ - EP, carbachol (Out), BRL 38227 (In): 6.19 +/- 0.14 vs 6.58 +/- 0.17]. 3 Removal of the epithelium did not affect the sensitivity to BRL 38227 (In) of preparations precontracted with a higher concentration (5 x 10(-6) M) of carbachol (Out). 4 In both + EP and - EP preparations precontracted with carbachol (10(-6) M; Out), BRL 38227 (In) had a more potent relaxant effect than aminophylline (In) (EC50, BRL 38227 vs aminophylline, + EP/ - EP: 5.93 +/- 0.06 vs 3.66 +/- 0.11/6.25 +/- 0.07 vs 3.77 +/- 0.11). 5 In preparations precontracted with carbachol (10(-6) m; Out), removal of the epithelium did not affect the sensitivity to aminophylline (In) but increased the degree of precontraction (T(max)) following epithelial but not serosal stimulation with carbachol. 6 We conclude that BRL 38227, a K+ channel activator, is a potent relaxant of rat tracheal smooth muscle precontracted with carbachol, and that the effect can be partially inhibited by the presence of an intact tracheal epithelium, whereas the relaxant effect of aminophylline is not.

引用

页码：139 / 144

页数：6

共 18 条

[1]

AKASAKA K, 1975, TOHOKU J EXP MED, V117, P55, DOI 10.1620/tjem.117.55

[2] EVALUATION OF THE POTASSIUM CHANNEL ACTIVATOR CROMAKALIM (BRL-34915) AS A BRONCHODILATOR IN THE GUINEA-PIG - COMPARISON WITH NIFEDIPINE [J].

ARCH, JRS ;

BUCKLE, DR ;

BUMSTEAD, J ;

CLARKE, GD ;

TAYLOR, JF ;

TAYLOR, SG .

BRITISH JOURNAL OF PHARMACOLOGY, 1988, 95 (03) :763-770

[3] POTASSIUM CHANNELS AND AIRWAY FUNCTION - NEW THERAPEUTIC PROSPECTS [J].

BLACK, JL ;

BARNES, PJ .

THORAX, 1990, 45 (03) :213-218

[4] THE ACTION OF A POTASSIUM CHANNEL ACTIVATOR, BRL-38227 (LEMAKALIM), ON HUMAN AIRWAY SMOOTH-MUSCLE [J].

BLACK, JL ;

ARMOUR, CL ;

JOHNSON, PRA ;

ALOUAN, LA ;

BARNES, PJ .

AMERICAN REVIEW OF RESPIRATORY DISEASE, 1990, 142 (06) :1384-1389

[5]

CUSS FM, 1987, AM REV RESPIR DIS, V136, P32

[6] CONTROL OF HUMAN AIRWAY SMOOTH-MUSCLE - INVITRO STUDIES [J].

DAVIS, C ;

KANNAN, MS ;

JONES, TR ;

DANIEL, EE .

JOURNAL OF APPLIED PHYSIOLOGY, 1982, 53 (05) :1080-1087

[7]

FEDAN JS, 1988, ASTHMA BASIC MECHANI

[8]

HALL A K, 1988, British Journal of Pharmacology, V95, p792P

[9]

ICHINOSE M, 1990, J PHARMACOL EXP THER, V252, P1207

[10] K-CHANNELS OF HUMAN ALVEOLAR MACROPHAGES [J].

KAKUTA, Y ;

OKAYAMA, H ;

AIKAWA, T ;

KANNO, T ;

OHYAMA, T ;

SASAKI, H ;

KATO, T ;

TAKISHIMA, T .

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1988, 81 (02) :460-468

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