Atrial natriuretic peptide and cyclic nucleotides affect glucose- induced Ca²⁺ responses in single pancreatic islet β-cells: Correlation with (Ca²⁺ + Mg²⁺)-ATPase activity

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 β- cells from isolated islets of rats maintained at 1.67 mmol/l glucose. ANP (1 nmol/1 to 1 μmol/l) inhibited the glucose (8.2 mmol/l)-induced phase 0 [Ca²⁺](i) 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 (Ca²⁺ 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 β-cells perhaps through mechanisms involving changes in SERCA activity and Ca²⁺ influx.