Effects of extracellular adenine nucleotides on the electrical, ionic and secretory events in mouse pancreatic β‐cells

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Abstract
1 The mechanisms whereby extracellular adenine nucleotides modulate pancreatic β-cell function were studied with mouse islets stimulated by 15 mm glucose. 2 Adenosine 5′-triphosphate (ATP) and adenosine 5′-diphosphate (ADP) (100 μm) inhibited insulin release, 45Ca efflux and 86Rb efflux from islet cells, and decreased electrical activity in β-cells. These changes were rapid but small and transient. 3 α,β-Methylene ADP caused a rapid and sustained inhibition of insulin release, 45Ca efflux and 86Rb efflux from islet cells. It also produced a slight hyperpolarization of the β-cell membrane, with sustained modification of the pattern but only transient decrease of the intensity of the electrical activity. In the absence of extracellular Ca2+, α,β-methylene ADP increased 45Ca and 86Rb efflux without changing insulin release. Most effects of α,β-methylene ATP were qualitatively similar but quantitatively smaller than those of the ADP-analogue. 4 Adenylylimido-diphosphate (AMP-PNP) slightly increased 45Ca and 86Rb efflux and potentiated insulin release in the presence of extracellular Ca2+. However, its effects on electrical activity in β-cells were qualitatively similar to those of the α,β-methylene analogues. 5 The small effects of ATP and ADP could result from their degradation into adenosine. α,β-Methylene ADP appears to increase K+ permeability of the β-cell membrane and to produce a second, intracellular, effect which largely contributes to the inhibition of insulin release. Another recognition site, with higher affinity for triphosphate derivatives, could mediate the small stimulatory effects of AMP-PNP.