Premium
Evidence that the mechanism of the inhibitory action of pinacidil in rat and guinea‐pig smooth muscle differs from that of glyceryl trinitrate
Author(s) -
Bray Katharine M.,
Newgreen D.T.,
Small R.C.,
Southerton J.S.,
Taylor S.G.,
Weir Sheila W.,
Weston A.H.
Publication year - 1987
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.1476-5381.1987.tb10297.x
Subject(s) - pinacidil , apamin , trachealis muscle , inhibitory postsynaptic potential , chemistry , pharmacology , taenia coli , myograph , medicine , biophysics , potassium channel , endocrinology , guinea pig , contraction (grammar) , charybdotoxin , biology , glibenclamide , diabetes mellitus
1 The effects of pinacidil have been compared with those of glyceryl trinitrate (GTN) using the aorta and portal vein of the rat and the trachealis and taenia caeci of the guinea‐pig. 2 In aorta, both pinacidil and GTN inhibited responses to noradrenaline and showed some selective inhibition of contractions to 20 m m K + . Responses to 80 m m K + were little affected. 3 In trachealis, both pinacidil and GTN inhibited spontaneous tone and selectively relaxed spasms to 20 m m K + . Responses to 80 m m K + were unaffected. 4 In portal vein, pinacidil completely inhibited spontaneous electrical and mechanical activity. GTN reduced the amplitude of tension waves and extracellularly‐recorded discharges, but increased the frequency of spontaneous electrical and mechanical activity. 5 In portal vein, pinacidil inhibited contractions to noradrenaline and selectively inhibited responses to 20 m m K + . GTN had little inhibitory effect on responses to either noradrenaline or K + . 6 In portal veins loaded with 86 Rb as a K + ‐marker, pinacidil significantly increased the 86 Rb efflux rate coefficient whilst GTN had no effect on 86 Rb exchange. 7 In taenia caeci, both pinacidil and GTN inhibited the spontaneous tone of the preparation. These inhibitory effects were not antagonized by apamin. 8 It is concluded that pinacidil and GTN do not share a common relaxant mechanism. Evidence has been obtained that pinacidil exerts its inhibitory effects by the opening of apamin‐insensitive, 86 Rb‐permeable K + channels.