Linked Life Data

9726229

Source:http://linkedlifedata.com/resource/pubmed/id/9726229

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1998-9-16
pubmed:abstractText
Sulfonylureas stimulate insulin secretion from pancreatic beta-cells by closing ATP-sensitive K+ (K(ATP)). The beta-cell and cardiac muscle K(ATP) channels have recently been cloned and shown to possess a common pore-forming subunit (Kir6.2) but different sulfonylurea receptor subunits (SUR1 and SUR2A, respectively). We examined the mechanism underlying the tissue specificity of the sulfonylureas tolbutamide and glibenclamide, and the benzamido-derivative meglitinide, using cloned beta-cell (Kir6.2/SUR1) and cardiac (Kir6.2/SUR2A) K(ATP) channels expressed in Xenopus oocytes. Tolbutamide inhibited Kir6.2/SUR1 (Ki approximately 5 micromol/l), but not Kir6.2/SUR2A, currents with high affinity. Meglitinide produced high-affinity inhibition of both Kir6.2/SUR1 and Kir6.2/SUR2A currents (Kis approximately 0.3 micromol/l and approximately 0.5 micromol/l, respectively). Glibenclamide also blocked Kir6.2/SUR1 and Kir6.2/SUR2A currents with high affinity (Kis approximately 4 nmol/l and approximately 27 nmol/l, respectively); however, only for cardiac-type K(ATP) channels was this block reversible. Physiological concentrations of MgADP (100 micromol/l) enhanced glibenclamide inhibition of Kir6.2/SUR1 currents but reduced that of Kir6.2/SUR2A currents. The results suggest that SUR1 may possess separate high-affinity binding sites for sulfonylurea and benzamido groups. SUR2A, however, either does not possess a binding site for the sulfonylurea group or is unable to translate the binding at this site into channel inhibition. Although MgADP reduces the inhibitory effect of glibenclamide on cardiac-type K(ATP) channels, drugs that bind to the common benzamido site have the potential to cause side effects on the heart.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0012-1797
pubmed:author
pubmed:issnType
Print
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1412-8
pubmed:dateRevised
2009-9-29
pubmed:meshHeading
pubmed-meshheading:9726229-ATP-Binding Cassette Transporters, pubmed-meshheading:9726229-Animals, pubmed-meshheading:9726229-Benzamides, pubmed-meshheading:9726229-Cloning, Molecular, pubmed-meshheading:9726229-Female, pubmed-meshheading:9726229-Glyburide, pubmed-meshheading:9726229-Heart, pubmed-meshheading:9726229-Hypoglycemic Agents, pubmed-meshheading:9726229-Islets of Langerhans, pubmed-meshheading:9726229-Membrane Potentials, pubmed-meshheading:9726229-Mice, pubmed-meshheading:9726229-Myocardium, pubmed-meshheading:9726229-Oocytes, pubmed-meshheading:9726229-Organ Specificity, pubmed-meshheading:9726229-Potassium Channels, pubmed-meshheading:9726229-Potassium Channels, Inwardly Rectifying, pubmed-meshheading:9726229-Rats, pubmed-meshheading:9726229-Receptors, Drug, pubmed-meshheading:9726229-Recombinant Proteins, pubmed-meshheading:9726229-Tolbutamide, pubmed-meshheading:9726229-Xenopus laevis
pubmed:year
1998
pubmed:articleTitle
Tissue specificity of sulfonylureas: studies on cloned cardiac and beta-cell K(ATP) channels.
pubmed:affiliation
University Laboratory of Physiology, Oxford, England, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't