title: Atrial natriuretic peptide and cyclic nucleotides affect glucose-induced Ca2+ responses in single pancreatic islet beta-cells: correlation with (Ca[2+] + Mg2+)-ATPase activity.
abstract: Glucose stimulation of pancreatic islets is characterized by an initial decline in intracellular Ca2+ concentration ([Ca2+]i) (phase 0), followed by an increase in peak [Ca2+]i (phase 1). The effect of atrial natriuretic peptide (ANP) and cyclic nucleotides on the glucose-induced phase 0 [Ca2+]i was investigated by Fura-2 fluorescent imaging in single beta-cells from isolated islets of rats maintained at 1.67 mmol/l glucose. ANP (1 nmol/l to 1 micromol/l) inhibited the glucose (8.2 mmol/l)-induced phase 0 [Ca2+], in a concentration-dependent manner. Forskolin, 8-bromo-cyclic AMP (8BrcAMP), and 8-bromo-cyclic guanosine monophosphate (8BrcGMP) also inhibited the glucose-induced phase 0 [Ca2+]i. The Ca2+ channel blocker, D 600, prevented the response to 8BrcAMP but not to ANP or 8BrcGMP on phase 0 [Ca2+]i. Thapsigargin (TG) also inhibited phase 0 [Ca2+]i by 90%. ANP, 8BrcGMP, and TG also reduced the time required for glucose to initiate the phase 1 increase in [Ca2+]i, and each of these agents potentiated the effect of glucose on peak [Ca2+]i. Furthermore, sarco(endo)-plasmic reticulum (Ca[2+] + Mg2+)-ATPase (SERCA) activity in RINm5F insulinoma cells was inhibited by 8BrcGMP and TG, but not 8BrcAMP. Thus, ANP and cGMP modulate [Ca2+]i regulation in pancreatic beta-cells perhaps through mechanisms involving changes in SERCA activity and Ca2+ influx.
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, 14214, USA.
authors.forename: B
authors.initials: B
authors.lastname: Lee
authors.forename: S G
authors.initials: SG
authors.lastname: Laychock
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D017301:Ca(2+) Mg(2+)-ATPase / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005711:Gallopamil / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009712:Nucleotides, Cyclic / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D009712:Nucleotides, Cyclic; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; D005711:Gallopamil; D019284:Thapsigargin; D009320:Atrial Natriuretic Factor; D017301:Ca(2+) Mg(2+)-ATPase; D006152:Cyclic GMP; D005947:Glucose; D002118:Calcium