Effects of extracellular adenine nucleotides on the electrical, ionic and secretory events in mouse pancreatic beta-cells.
1. The mechanisms whereby extracellular adenine nucleotides modulate pancreatic beta-cell function were studied with mouse islets stimulated by 15 mM glucose. 2. Adenosine 5'-triphosphate (ATP) and adenosine 5'-diphosphate (ADP) (100 microM) inhibited insulin release, 45Ca efflux and 86Rb efflux from islet cells, and decreased electrical activity in beta-cells. These changes were rapid but small and transient. 3. alpha,beta-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 beta-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+, alpha,beta-methylene ADP increased 45Ca and 86Rb efflux without changing insulin release. Most effects of alpha,beta-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 beta-cells were qualitatively similar to those of the alpha,beta-methylene analogues. 5. The small effects of ATP and ADP could result from their degradation into adenosine. alpha,beta-Methylene ADP appears to increase K+ permeability of the beta-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.
Petit
P
P
I Physiologisches Institut, University of Saarland, Homburg/Saar, Germany.
Bertrand
G
G
Schmeer
W
W
Henquin
J C
JC
D000227:Adenine Nucleotides / Q000494:pharmacology*; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002132:Calcium Radioisotopes; D004594:Electrophysiology; D005260:Female; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D012414:Rubidium Radioisotopes
D000227:Adenine Nucleotides; D002132:Calcium Radioisotopes; D007328:Insulin; D012414:Rubidium Radioisotopes; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate