title: Antidiabetic sulphonylureas stimulate acetylcholine release from striatal cholinergic interneurones through inhibition of K(ATP) channel activity.
abstract: The sulphonylureas tolbutamide and glibenclamide were shown to stimulate acetylcholine release from rat striatal slices. To determine the mechanism of this effect, whole-cell patch-clamp recordings were made from large neurones within the striatum that displayed morphological, electrophysiological, and pharmacological characteristics typical of cholinergic interneurones. Dialysis of these neurones with a pipette solution containing low concentrations of ATP produced a gradual hyperpolarisation that could be reversed by bath application of the sulphonylureas. In voltage-clamp studies, these compounds were shown to act through the inhibition of a potassium conductance. It is concluded that cholinergic interneurones within the rat striatum express sulphonylurea-sensitive ATP-sensitive potassium channel activity. These channels are probably cytoprotective and may prove to be novel sites of therapeutic modulation.
authors.affiliation: Parke Davis Neuroscience Research Centre, Cambridge University Forvie Site, England.
authors.forename: K
authors.initials: K
authors.lastname: Lee
authors.forename: V
authors.initials: V
authors.lastname: Brownhill
authors.forename: P J
authors.initials: PJ
authors.lastname: Richardson
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D008297:Male; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014044:Tolbutamide / Q000494:pharmacology
chemical_list: D007004:Hypoglycemic Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D000109:Acetylcholine; D005905:Glyburide