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Imidazoline antagonists of α 2 ‐adrenoceptors increase insulin release in vitro by inhibiting ATP‐sensitive K + channels in pancreatic β‐cells
Author(s) -
Jonas J.C.,
Plant T.D.,
Henquin J.C.
Publication year - 1992
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.1476-5381.1992.tb14456.x
Subject(s) - diazoxide , imidazoline receptor , phentolamine , chemistry , tolazoline , endocrinology , medicine , insulin , adenosine triphosphate , idazoxan , propranolol , pharmacology , prazosin , antagonist , biochemistry , biology , receptor
1 Islets from normal mice were used to study the mechanisms by which imidazoline antagonists of α 2 ‐adrenoceptors increase insulin release in vitro . 2 Alinidine, antazoline, phentolamine and tolazoline inhibited 86 Rb efflux from islets perifused with a medium containing 3 m m glucose, i.e. under conditions where many adenosine 5′‐triphosphate (ATP)‐sensitive K + channels are open in the β‐cell membrane. They also reduced the acceleration of 86 Rb efflux caused by diazoxide, an opener of ATP‐sensitive K + channels. 3 ATP‐sensitive and voltage‐sensitive K + currents were measured in single β‐cells by the whole‐cell mode of the patch‐clamp technique. Antazoline more markedly inhibited the ATP‐sensitive than the voltage‐sensitive current, an effect previously observed with phentolamine. Alinidine and tolazoline partially decreased the ATP‐sensitive K + current. 4 The four imidazolines reversed the inhibition of insulin release caused by diazoxide (through opening of ATP‐sensitive K + channels) or by clonidine (through activation of α 2 ‐adrenoceptors) in a concentration‐dependent manner. Only the former effect correlated with the ability of each drug to increase control insulin release stimulated by 15 m m glucose alone. 5 It is concluded that the ability of imidazoline antagonists of α 2 ‐adrenoceptors to increase insulin release in vitro can be ascribed to their blockade of ATP‐sensitive K + channels in β‐cells rather than to their interaction with the adrenoceptor.