Regulation of ATP-sensitive K+ channels by chronic glyburide and pinacidil administration.
Treatment of rats with the K(ATP)+ channel antagonist sulfonylurea, glyburide (3 mg/kg/day, i.p., every 12 hr for 9 days), increased the Bmax value of [3H]glyburide binding to heart and whole brain total membranes by 30 and 24%, respectively. The ligand affinity was unaltered. Treatment with the K+ channel activator, pinacidil (20 mg/kg/day, i.p., every 12 hr for 9 days), did not alter the Bmax value for cardiac [3H]glyburide binding sites, but decreased the Bmax value in the brain by 21%. Chronic administration of hydralazine, which caused an acute reduction in systolic blood pressure equivalent to that of pinacidil, did not alter [3H]glyburide binding in either heart or brain. Treatment with glyburide, pinacidil or hydralazine did not alter L-type calcium channels, assessed by [3H]PN 200 110 binding, in cardiac and brain membranes or small size Ca(2+)-activated K+ channels in brain assessed by [125I]apamin binding. These studies show that the ATP-sensitive class of K+ channels can be regulated following chronic drug treatment in similar fashion to other receptor and channel systems.
Gopalakrishnan
M
M
Department of Biochemical Pharmacology, School of Pharmacy State University of New York, Buffalo 14260.
Triggle
D J
DJ
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D001030:Apamin / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007457:Iodine Radioisotopes; D017275:Isradipine / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D013997:Time Factors; D014316:Tritium; D014665:Vasodilator Agents / Q000494:pharmacology*
D015220:Calcium Channels; D006146:Guanidines; D007457:Iodine Radioisotopes; D015221:Potassium Channels; D014665:Vasodilator Agents; D014316:Tritium; D001030:Apamin; D020110:Pinacidil; D000255:Adenosine Triphosphate; D005905:Glyburide; D002118:Calcium; D017275:Isradipine