Cytosolic ADP enhances the sensitivity to tolbutamide of ATP-dependent K+ channels from pancreatic B-cells.
The effects of intracellular purine nucleotides on tolbutamide-induced block of ATP-dependent K+ channels from mouse pancreatic B-cells were studied using the patch-clamp technique. When applied to the inside of excised patches, tolbutamide alone blocked channel activity half-maximally at 55 microM and the concentration-response curve for the inhibition of K+ channels by tolbutamide was flat. ADP (1 mM), but not other nucleotides (AMP, GTP or GDP) increased the steepness of the concentration-response curve and decreased the half-maximally effective tolbutamide concentration to 4.2 microM. It is suggested that the ATP-dependent K+ channel or a closely related structure contains a receptor which is accessible for cytosolic ADP and controls the sensitivity to tolbutamide.
D000244:Adenosine Diphosphate / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D007515:Islets of Langerhans / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D014044:Tolbutamide / Q000494:pharmacology*
D015221:Potassium Channels; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D014044:Tolbutamide