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PMID: 2333295 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

K+ channel openers activate brain sulfonylurea-sensitive K+ channels and block neurosecretion.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 87 ·No. 9 ·1990-05-00 ·Pages 3489-92

Schmid-Antomarchi H, Amoroso S, Fosset M, Lazdunski M

Abstract

Vascular K+ channel openers such as cromakalim, nicorandil, and pinacidil potently stimulate 86Rb+ efflux from slices of substantia nigra. This 86Rb+ efflux is blocked by antidiabetic sulfonylureas, which are known to be potent and specific blockers of ATP-regulated K+ channels in pancreatic beta cells, cardiac cells, and smooth muscle cells. K0.5, the half-maximal effect of the enantiomer (-)-cromakalim, is as low as 10 nM, whereas K0.5 for nicorandil is 100 nM. These two compounds appear to have a much higher affinity for nerve cells than for smooth muscle cells. Openers of sulfonylurea-sensitive K+ channels lead to inhibition of gamma-aminobutyric acid release. There is an excellent relationship between potency to activate 86Rb+ efflux and potency to inhibit neurotransmitter release.

MeSH Terms
Animals Benzopyrans/pharmacology Brain/drug effects,physiology Cromakalim Hypoglycemic Agents/pharmacology In Vitro Techniques Kinetics Potassium Channels/drug effects,physiology Pyrroles/pharmacology Rats Rats, Inbred Strains Rubidium/metabolism Structure-Activity Relationship Sulfonylurea Compounds/pharmacology gamma-Aminobutyric Acid/metabolism
Chemicals
Benzopyrans Hypoglycemic Agents Potassium Channels Pyrroles Sulfonylurea Compounds Cromakalim gamma-Aminobutyric Acid Rubidium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Schmid-Antomarchi H
Institut de Pharmacologie Moléculaire et Cellulaire, UPR 411 Centre National de la Recherche Scientifique, Valbonne, France.
Amoroso S
Fosset M
Lazdunski M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.87.9.3489
Published
1990-05-00
Pages
3489-92
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC53926
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.87.9.3489 PMC Full Text View journal details
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