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Cell Calcium. 1995 Nov;18(5):411-9.

A cADP-ribose antagonist does not inhibit secretagogue-, caffeine- and nitric oxide-induced Ca2+ responses in rat pancreatic beta-cells.

Author information

1
Department of Pharmacology, University of Oxford, UK.

Abstract

It is controversial whether the Ca2+ mobilizing agent, cADP-ribose (cADPR), is implicated in secretagogue-mediated intracellular Ca2+ responses of pancreatic beta-cells. In this study we utilised a potent antagonist of cADPR, 8-amino-cADPR, to determine whether cADPR is involved in glucose-, acetylcholine-, caffeine- and nitric oxide-induced intracellular Ca2+ responses of isolated rat beta-cells. The antagonist was found to be effective in the complete inhibition of cADPR-induced Ca2+ release from sea urchin egg microsome preparations, when used at equivalent concentrations to cADPR (between 0.1-10 microM) in the assay. Isolated beta-cells were co-loaded with up to 50 microM 8-amino-cADPR, and Fura-2 or Fluo-3, by the whole-cell patch technique. At this concentration, the antagonist failed to affect standard glucose- and acetylcholine-induced increases in the intracellular free Ca2+ ([Ca2+]i) of isolated rat pancreatic beta-cells, as assessed by video ratio imaging and single wavelength microfluorimetry. Applying the same methodology, the antagonist also failed to affect NO- and caffeine-induced intracellular Ca2+ responses of rat beta-cells. These results suggest that cADPR does not appear to play a fundamental role in beta-cell Ca2+ signalling. As a control, patch-loading with heparin (2 mg/ml) however, abolished the acetylcholine response but neither affected the NO- or caffeine-induced mobilization of intracellular Ca2+. These results support the involvement of the IP3-receptor in acetylcholine-induced mobilization of intracellular Ca2+, but not that invoked by caffeine.

PMID:
8581969
DOI:
10.1016/0143-4160(95)90056-x
[Indexed for MEDLINE]

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