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  • 1
    ISSN: 1432-1424
    Keywords: Key words: cAMP — Calmodulin antagonist — Caged Ca2+— Islet of Langerhans — Glycogenolysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Abstract. Glucagon is known to increase intracellular cAMP levels and enhance glucose-induced electrical activity and insulin secretion in pancreatic β-cell perfused with Krebs-Ringer bicarbonate solution. The present experiments were aimed at evaluation of the hypothesis that changes in β-cells ATP-sensitive K+ (K(ATP)) channel activity are involved in the glucagon-induced enhancement of electrical activity. Channel activity was recorded using the cell-attached configuration of the patch-clamp technique. Addition of glucagon (2.9 × 10−7 m) in the presence of 11.1 mm glucose caused closure of K(ATP) channels followed by an increase in the frequency of biphasic current transients (action currents) due to action potential generation in the cell. Three calmodulin-antagonists (W-7, chlorpromazine, and trifluoperazine) restored with similar efficacy K(ATP) channel activity in cells being exposed to glucagon. At 2.8 mm glucose, glucagon did not affect K(ATP) channel activity until Ca2+ was released from Nitr-5 by flash photolysis, at which point channel activity was transiently suppressed. Similar effects were seen when db-cAMP was used instead of glucagon.These results support the view that glucagon and other cAMP-generating agonists enhance glucose-induced β-cell electrical activity through a Ca2+/calmodulin dependent-closure of K(ATP) channels.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1420-908X
    Keywords: Key words: Tripterygium wilfordii Hook F — Cyclooxygenase-2 — Glucocorticoid receptor — Nuclear factor-κB — Synovial cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Objective: Several extracts of Tripterygium wilfordii Hook F (TWHF) have been reported to be effective in patients with rheumatoid arthritis. We investigated the effect of multi-glycosides of TWHF (GTW), a TWHF extract, on interleukin (IL)-1β-stimulated human rheumatoid synovial cells. ¶Materials and Methods: IL-1β-stimulated synovial cells were used to detect the effects of GTW on cyclooxygenase (COX)-1 and COX-2 activities, expression of COX protein and mRNA, and nuclear transcription factors in experiments using respective reporter plasmids. ¶Results: GTW inhibited prostaglandin E2 production by IL-1β-stimulated synovial cells in a concentration-dependent manner, and also inhibited COX-2 protein and mRNA expression in a similar fashion to dexamethasone. However, GTW did not act as a glucocorticoid agonist. GTW repressed IL-1β-induced nuclear factor-κB activity, but did not have a significant influence on activating protein-1 activity. ¶Conclusion: The anti-rheumatic effect of GTW or TWHF may be partly mediated through the inhibition of prostaglandin E2 production in human synovial cells due to suppression of COX-2 mRNA, possibly via inhibition of nuclear factor-κB activity.
    Type of Medium: Electronic Resource
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