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Influence of epithelium on the inhibition of melittin‐induced contraction of guinea‐pig isolated trachea by the potassium channel opener NIP‐121
Author(s) -
Shikada Kenichi,
Tanaka Sakuya
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13734.x
Subject(s) - melittin , isoprenaline , chemistry , aminophylline , glibenclamide , contraction (grammar) , endocrinology , epithelium , medicine , trachealis muscle , propranolol , pharmacology , potassium channel , biochemistry , stimulation , biology , charybdotoxin , genetics , diabetes mellitus , peptide
1 We have investigated the effect of the potassium channel opener, NIP‐121, on contraction elicited by melittin (a phospholipase A 2 activator) in epithelium‐intact and epithelium‐denuded trachea isolated from guinea‐pigs. The effects of NIP‐121 were compared with those of isoprenaline, aminophylline and hydrocortisone. 2 In the presence of the cyclo‐oxygenase inhibitor, indomethacin (5 μ m ), melittin (3 μg ml −1 ) caused time‐dependent contraction. The melittin‐induced contractile response was significantly augmented by removal of the epithelium and was concentration‐dependently and completely inhibited by the phospholipase A 2 (PLA 2 ) inhibitor, p ‐bromophenacyl bromide (BPB 10–100 μ m ), and the lipoxygenase inhibitor, phenidone (10–300 μ m ). Similar inhibition of the melittin response by BPB (10 μ m ) and phenidone (10 μ m ) was observed in the epithelium‐denuded trachea. 3 Concentration‐dependent inhibition of the melittin response was induced by preincubation with NIP‐121 (0.03 and 0.1 μ m ), isoprenaline (0.001 and 0.01 μ m ), aminophylline (30 and 100 μ m ) and hydrocortisone (100 and 300 μ m ). The effect of NIP‐121 was abolished by glibenclamide (1 μ m ). 4 The inhibitory effect of NIP‐121 on the melittin response was greatly reduced by removing the epithelium while that of the isoprenaline, aminophylline or hydrocortisone was not changed. 5 The inhibition of the melittin response by these drugs was similar to their inhibition of the contraction elicited by a low concentration (3 n m ) of leukotriene D 4 (LTD 4 ) in the epithelium‐intact trachea. Inhibition of the LTD 4 response by NIP‐121 was not observed in the epithelium‐denuded trachea. However, higher concentrations of NIP‐121 (0.3 and 1 μ m ) did inhibit LTD 4 ‐induced contractions of epithelium‐denuded trachea. 6 These findings suggest that melittin causes epithelium‐dependent contraction of the guinea‐pig isolated trachea which is mediated by products of lipoxygenase activity. NIP‐121 may inhibit the melittin response by activating glibenclamide‐sensitive potassium channels, which appear to be epithelium‐dependent (an indirect effect of NIP‐121 apart from its direct effect on the airway smooth muscle) while isoprenaline, aminophylline and hydrocortisone act directly to relax the trachealis smooth muscle.