ATRIAL-NATRIURETIC-PEPTIDE AND CYCLIC-NUCLEOTIDES AFFECT GLUCOSE-INDUCED CA2-ISLET BETA-CELLS - CORRELATION WITH (CA2++MG2+)-ATPASE ACTIVITY( RESPONSES IN SINGLE PANCREATIC)

Glucose stimulation of pancreatic islets is characterized by an initia l decline in intracellular Ca2+ concentration ([Ca2+](i)) (phase 0), f ollowed by an increase in peak [Ca2+](i) (phase 1). The effect of atri al natriuretic peptide (ANP) and cyclic nucleotides on the glucose-ind uced phase 0 [Ca2+](i) was investigated by Fura-2 fluorescent imaging in single beta-cells from isolated islets of rats maintained at 1.67 m mol/l glucose. ANP (1 mmol/l to 1 mu mol/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 guanosin e monophosphate (8BrcGMP) also inhibited the glucose-induced phase 0 [ Ca2+](i). The Ca2+ channel blocker, D 600, prevented the response to 8 BrcAMP but not to ANP or 8BrcGMP on phase 0 [Ca2+](i). Thapsigargin (T G) also inhibited phase 0 [Ca2+](i) by 90%. ANP, 8BrcGMP and TG also r educed the time required for glucose to initiate the phase 1 increase in [Ca2+](i) and each of these agents potentiated the effect of glucos e on peak [Ca2+](i). Furthermore, sarco(endo)-plasmic reticulum (Ca2+ Mg2+)-ATPase (SERCA) activity in RINm5F insulinoma cells was inhibit ed by 8BrcGMP and TG but not 8BrcAMP. Thus, ANP and cGMP modulate [Ca2 +](i) regulation in pancreatic beta-cells perhaps through mechanisms i nvolving changes in SERCA activity and Ca2+ influx.