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

Journal Article · Tue May 01 04:00:00 EDT 1990 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.87.9.3489· OSTI ID:5463754

Schmid-Antomarchi, H; Amoroso, S; Fosset, M; Lazdunski, M ^[1]

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1. Centre National de la Recherche Scientifique, Valbonne (France)

Vascular K{sup +} channel openers such as cromakalim, nicorandil, and pinacidil potently stimulate {sup 86}Rb{sup +} efflux from slices of substantia nigra. This {sup 86}Rb{sup +} efflux is blocked by antidiabetic sulfonylureas, which are known to be potent and specific blockers of ATP-regulated K{sup +} channels in pancreatic beta cells, cardiac cells, and smooth muscle cells. K{sub 0.5}, the half-maximal effect of the enantiomer ({minus})-cromakalim, is as low as 10 nM, whereas K{sub 0.5} 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{sup +} channels lead to inhibition of {gamma}-aminobutyric acid release. There is an excellent relationship between potency to activate {sup 86}Rb{sup +} efflux and potency to inhibit neurotransmitter release.

• OSTI ID: 5463754
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 87:9; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALI METAL COMPOUNDS
AMIDES
AMINO ACIDS
AMINOBUTYRIC ACID
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BODY
BRAIN
CARBONIC ACID DERIVATIVES
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CHLORIDES
CHLORINE COMPOUNDS
DAYS LIVING RADIOISOTOPES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
HALIDES
HALOGEN COMPOUNDS
HYDROGEN COMPOUNDS
INHIBITION
INTERMEDIATE MASS NUCLEI
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
MEMBRANE PROTEINS
MEMBRANE TRANSPORT
MINUTES LIVING RADIOISOTOPES
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ODD-ODD NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
POTASSIUM COMPOUNDS
PROTEINS
RADIOISOTOPES
RECEPTORS
RUBIDIUM 86
RUBIDIUM CHLORIDES
RUBIDIUM COMPOUNDS
RUBIDIUM ISOTOP
TRITIUM COMPOUNDS
UREA