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Insulin and glucagon attenuate the ability of cholera toxin to activate adenylate cyclase in intact hepatocytes.

ABSTRACT: Treatment of intact hepatocytes with cholera toxin at 37 degrees C caused a stable activation of adenylate cyclase activity after a lag period of around 10 min. The presence of either insulin (10 nM) or glucagon (10 nM) in the incubation medium had little effect on this lag period; however, these hormones markedly attenuated the maximal activation of adenylate cyclase activity that could be achieved by treatment with cholera toxin. Such actions of insulin and glucagon were dose-dependent, with EC50 values (concn. giving 50% inhibition) of 0.20 nM for insulin and 0.49 nM for glucagon, and were not additive. Treatment of intact hepatocytes with either glucagon or insulin did not affect the ability of cholera toxin to cause the ADP-ribosylation of the 45 kDa alpha-subunit of the stimulatory guanine nucleotide regulatory protein, Gs, in intact hepatocytes. It is suggested that treatment of intact hepatocytes with either insulin or glucagon attenuates the stimulatory action of ADP-ribosylated Gs on adenylate cyclase.

SUBMITTER: Irvine FJ

PROVIDER: S-EPMC1149023 | biostudies-other | 1988 Apr

REPOSITORIES: biostudies-other

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The action of islet activating protein (pertussis toxin) on insulin's ability to inhibit adenylate cyclase and activate cyclic AMP phosphodiesterases in hepatocytes.

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Cholera toxin requires oxidized nicotinamide-adenine dinucleotide to activate adenylate cyclase in purified rat liver plasma membranes.

Project description:Activation of adenylate cyclase in isolated rat liver plasma membranes by cholera toxin was demonstrated. The activation requires the presence of NAD+ and ATP and is irreversible.

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Transcriptional responses of murine macrophages to the adenylate cyclase toxin of Bordetella pertussis

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Adenylate Cyclase Toxin promotes bacterial internalisation into non phagocytic cells.

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Bordetella pertussis adenylate cyclase toxin translocation across a tethered lipid bilayer.

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Adenylyl Cyclase 6 Expression Is Essential for Cholera Toxin-Induced Diarrhea.

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Transcriptional responses of murine macrophages to the adenylate cyclase toxin of Bordetella pertussis

2013-09-22 | E-GEOD-51075 | biostudies-arrayexpress

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Challenge of hepatocytes by glucagon triggers a rapid modulation of adenylate cyclase activity in isolated membranes.

Project description:Membrane fractions obtained from hepatocytes treated with glucagon exhibited a decreased glucagon (with or without GTP)-stimulated adenylate cyclase activity. A maximum effect was seen in around 5 min. No change in the rate of cyclic AMP production was observed for the basal, NaF-, p[NH]ppG (guanosine 5'-[beta, gamma-imido]-triphosphate)- and GTP-stimulated states of the enzyme. The lag observed in the p[NH]ppG-stimulated adenylate cyclase activity of native membranes was abolished when membranes from glucagon-pretreated cells were used. When Mn2+ replaced Mg2+ in the assays, the magnitude of the apparent desensitization was decreased. Mn2+ abolished the lag of onset of p[NH]ppG-stimulated activity in native membranes. The desensitization process was dose-dependent on glucagon, which exhibited a Ka of 4 X 10(-10) M. Depletion of intracellular ATP did not affect this process. It is suggested that this desensitization occurs at the level of the guanine nucleotide-regulatory protein.

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