Antidiabetic sulphonylureas stimulate acetylcholine release from striatal cholinergic interneurones through inhibition of K(ATP) channel activity.
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.
Lee
K
K
Parke Davis Neuroscience Research Centre, Cambridge University Forvie Site, England.
Brownhill
V
V
Richardson
P J
PJ
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
D007004:Hypoglycemic Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D000109:Acetylcholine; D005905:Glyburide