title: The neurotransmitter ATP triggers Ca2+ responses promoting coordination of pancreatic islet oscillations.
abstract: OBJECTIVE
  Pulsatile insulin release into the portal vein is critically dependent on entrainment of the islets in the pancreas into a common oscillatory phase. Because the pulses reflect periodic variations of the cytoplasmic Ca concentration ([Ca]i), we studied whether the neurotransmitters adenosine triphosphate (ATP) and acetylcholine promote synchronization of [Ca]i oscillations between islets lacking contact.
  
  
  METHODS
  Medium-sized and small mouse islets and cell aggregates were used for measuring [Ca]i with the indicator fura-2.
  
  
  RESULTS
  Exposure to acetylcholine resulted in an initial [Ca]i peak followed by disappearance of the [Ca]i oscillations induced by 11-mmol/L glucose. The effect of ATP was often restricted to an elusive [Ca]i peak. The incidence of distinct [Ca]i responses to ATP increased under conditions (accelerated superfusion, small islets, or cell aggregates) intended to counteract purinoceptor desensitization owing to intercellular accumulation of ATP. Attempts to imitate neural activity by brief (15 seconds) exposure to ATP or acetylcholine resulted in temporary synchronization of the glucose-induced [Ca]i oscillations between islets lacking contact.
  
  
  CONCLUSIONS
  The data support the idea that purinergic signaling has a key role for coordinating the oscillatory activity of the islets in the pancreas, reinforcing previous arguments for the involvement of nonadrenergic, noncholinergic neurons.
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Gylfe
authors.forename: Eva
authors.initials: E
authors.lastname: Grapengiesser
authors.forename: Heléne
authors.initials: H
authors.lastname: Dansk
authors.forename: Bo
authors.initials: B
authors.lastname: Hellman
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D020013:Calcium Signaling; D003593:Cytoplasm / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005947:Glucose / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009765:Obesity / Q000378:metabolism; D013997:Time Factors; D046509:Tissue Culture Techniques
chemical_list: D000255:Adenosine Triphosphate; D005947:Glucose; D000109:Acetylcholine