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Effects of putative activators of K + channels in mouse pancreatic β‐cells
Author(s) -
Garrino M.G.,
Plant T.D.,
Henquin J.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.tb14626.x
Subject(s) - diazoxide , pinacidil , cromakalim , nicorandil , minoxidil , glibenclamide , medicine , endocrinology , potassium channel opener , chemistry , potassium channel , pharmacology , insulin , diabetes mellitus
1 The vasodilator and antihypertensive properties of pinacidil, cromakalim (BRL 34915), nicorandil and minoxidil sulphate may be due, at least in part, to their ability to open K + channels in vascular smooth muscles. In this study, mouse pancreatic islets were used to determine whether these drugs affect insulin release by acting on K + channels of β‐cells. Their effects were compared to those of diazoxide. 2 Diazoxide caused a dose‐dependent inhibition of insulin release by islets incubated with 15 m m glucose (93% at 100 μ m ). Pinacidil inhibited release by 36 and 72% at 100 and 500 μ m , respectively. Cromakalim and nicorandil were less effective (35 and 25% inhibition at 500 μ m ). Minoxidil sulphate increased insulin release at 500 μ m . 3 In the presence of 7 m m glucose and in the absence of Ca 2+ (to avoid activation of Ca 2+ ‐dependent K + channels), 86 Rb efflux from islet cells was increased by 100–500 μ m pinacidil and 500 μ m nicorandil, which were, however, less potent than diazoxide. Cromakalim was ineffective, whereas 500 μ m minoxidil sulphate decreased the efflux rate. In the absence of glucose and presence of Ca 2+ , 500 μ m cromakalim and minoxidil sulphate inhibited 86 Rb efflux. 4 Like diazoxide, pinacidil (500 μ m ) abolished glucose‐induced electrical activity in β‐cells and hyperpolarized the membrane. 5 ATP‐sensitive K + currents were studied in single β‐cells by the whole cell patch‐clamp technique. Pinacidil increased the current less than did diazoxide. In contrast, cromakalim and minoxidil sulphate decreased K + ‐currents whilst nicorandil was without effect. 6 It is concluded that pinacidil, like diazoxide, inhibits insulin release from β‐cells by opening ATP‐sensitive K + channels, whereas the smaller inhibitory effects of cromakalim and nicorandil may involve actions other than on K + channels in these cells. Minoxidil sulphate potentiates glucose‐induced insulin release, probably by inhibiting ATP‐sensitive K + channels. However, all these effects of the vasodilators are only seen at high concentrations and are thus unlikely to occur in vivo .