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-cells
Department of Pharmacology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka City, Shizuoka 422-8526, Japan
In
isolated rat pancreatic 
-cells, the nitric oxide (NO) donor NOC-7 at
1 µM reduced the amplitude of the oscillations of cytosolic
Ca2+ concentration ([Ca2+]c)
induced by 11.1 mM glucose, and at 10 µM terminated them. In the
presence of NG-nitro-L-arginine
(L-NNA), however, NOC-7 at 0.5 and 1 µM increased the
amplitude of the [Ca2+]c oscillations,
although the NO donor at 10 µM still suppressed them. Aqueous NO
solution also had a dual effect on the
[Ca2+]c oscillations. The soluble guanylate
cyclase inhibitor LY-83583 and the cGMP-dependent protein kinase
inhibitor KT5823 inhibited the stimulatory effect of NO, and
8-bromo-cGMP increased the amplitude of the
[Ca2+]c oscillations. Patch-clamp analyses in
the perforated configuration showed that 8-bromo-cGMP inhibited whole
cell ATP-sensitive K+ currents in the isolated rat
pancreatic -cells, suggesting that the inhibition by cGMP of
ATP-sensitive K+ channels is, at least in part, responsible
for the stimulatory effect of NO on the
[Ca2+]c oscillations. In the presence of
L-NNA, the glucose-induced insulin secretion from isolated
islets was facilitated by 0.5 µM NOC-7, whereas it was suppressed by
10 µM NOC-7. These results suggest that NO facilitates
glucose-induced [Ca2+]c oscillations of
-cells and insulin secretion at low concentrations, which effects
are mediated by cGMP, whereas NO inhibits them in a cGMP-independent
manner at high concentrations.
islets of Langerhans; calcium oscillations; guanosine 3',5'-cyclic monophosphate; NOC-7; glucose
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