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. 1994 Jan;111(1):302–310. doi: 10.1111/j.1476-5381.1994.tb14060.x

Interaction of tolbutamide and cytosolic nucleotides in controlling the ATP-sensitive K+ channel in mouse beta-cells.

C Schwanstecher 1, C Dickel 1, U Panten 1
PMCID: PMC1910016  PMID: 8012711

Abstract

1. In mouse pancreatic beta-cells the role of cytosolic nucleotides in the regulation of the sulphonylurea sensitivity of the adenosine 5'-triphosphate-sensitive K+ channel (KATP-channel) was examined. Patch-clamp experiments with excised inside-out membrane patches were carried out using an experimental protocol favouring phosphorylation of membrane proteins. 2. In the absence of Mg2+, the KATP-channel-inhibiting potency of cytosolic nucleotides decreased in the order ATP = adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) > adenosine 5'-diphosphate (ADP) > adenosine 5'-O-(2-thiodiphosphate) (ADP beta S) = adenylyl-imidodiphosphate (AMP-PNP) > 2'-deoxyadenosine 5'-triphosphate (dATP) > uridine 5'-triphosphate (UTP) > 2'-deoxyadenosine 5'-diphosphate (dADP) > guanosine 5'-triphosphate (GTP) > guanosine 5'-diphosphate (GDP) > uridine 5'-diphosphate (UDP). 3. In the presence of Mg2+, the inhibitory potency of cytosolic nucleotides decreased in the order ATP gamma S > ATP > AMP-PNP > ADP beta S > dATP > UTP. In the presence of Mg2+, the KATP-channels were activated by dADP, GTP, GDP and UDP. 4. Tolbutamide inhibited the KATP-channels not only in the presence but also in the prolonged absence of Mg2+. In nucleotide-free solutions, the potency of tolbutamide was very low. When about half of the KATP-channel activity was inhibited by ATP, AMP-PNP, ADP beta S or ADP (absence of Mg2+), the potency of tolbutamide was increased. 5. Tolbutamide (100 microM) slightly enhanced the channel-inhibiting potency of AMP-PNP and inhibited the channel-activating effect of MgGDP in a non-competitive manner.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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