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Cromakalim‐induced relaxation of guinea‐pig isolated trachealis: antagonism by glibenclamide and by phentolamine
Author(s) -
Murray M.A.,
Boyle J.P.,
Small R.C.
Publication year - 1989
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.1476-5381.1989.tb14615.x
Subject(s) - phentolamine , cromakalim , glibenclamide , isoprenaline , yohimbine , prazosin , chemistry , medicine , endocrinology , aminophylline , trachealis muscle , theophylline , propranolol , potassium channel , pharmacology , stimulation , diabetes mellitus , charybdotoxin , receptor , antagonist
1 Tested against the spontaneous tone of guinea‐pig isolated trachealis, cromakalim (0.1–100 μ m ), isoprenaline (1 n m ‐1 μ m ) and theophylline (1 μ m ‐1 m m ) each produced concentration‐dependent relaxation. 2 Glibenclamide (0.1–10 μ m ) did not itself alter the spontaneous tone of the trachea nor did it modify the relaxant actions of isoprenaline or theophylline. In contrast, glibenclamide (0.1 and 1 μ m ) caused a concentration‐dependent rightward shift of the log concentration‐effect curve of cromakalim. Glibenclamide (10 μ m ) reduced the slope of the log concentration‐effect curve of cromakalim and moved the foot of the curve back towards the control position. 3 Phentolamine (1, 10 and 100 μ m ) did not itself alter the spontaneous tone of the trachea nor did it modify the relaxant actions of isoprenaline or theophylline. In contrast phentolamine caused concentration‐dependent depression of the log concentration‐effect curve of cromakalim. 4 Neither prazosin (1 μ m ) nor yohimbine (10 μ m ) modified the spontaneous tone of the trachea. Prazosin and yohimbine each failed to antagonise the effects of cromakalim, isoprenaline and theophylline. 5 Intracellular electrophysiological recording showed that glibenclamide (1 μ m ) and phentolamine (100 μ m ) caused minor change in the resting membrane potential of trachealis cells. Slow wave activity was slightly depressed by these agents. In contrast tetraethylammonium (TEA; 8 m m ) caused marked depolarisation, and promoted the conversion of slow waves into regenerative action potentials. These electrical changes were accompanied by tonic tension development. 6 Phentolamine (100 μ m ) and glibenclamide (1 μ m ) reduced and reversed both the relaxation and the hyperpolarisation induced by cromakalim (10 μ m ). 7 It is concluded that glibenclamide and phentolamine each provide selective antagonism of the relaxant action of cromakalim in guinea‐pig trachealis. These agents also inhibit the plasmalemmal hyperpolarisation induced by cromakalim. The effect of phentolamine is unrelated to the blockade of α 1 or α 2 ‐adrenoceptors. If either glibenclamide or phentolamine act to block the K + channels opened by cromakalim, then such channels are not identical to those which endow the trachealis plasmalemma with its powerful rectifying behaviour.