Cytosolic free-calcium concentrations in normal pancreatic islet cells. Effect of secretagogues and somatostatin.
We have assessed the effect of somatostatin on glucose-, potassium-, forskolin-, and dibutyryl cAMP-induced changes in cytosolic free [Ca2+] in normal rat pancreatic islet cells with the new Ca2+ indicator fura 2. The cytosolic free [Ca2+] in islet cells incubated with nonstimulatory concentrations of glucose (30 mg/dl) ranged from 54 to 64 nM. In the presence of extracellular Ca2+ (1 mM), glucose (300 mg/dl) rapidly increased the cytosolic free [Ca2+] to a level of 90-110 nM. In the absence of extracellular Ca2+, glucose failed to increase the cytosolic free [Ca2+], which remained at a level of 55-60 nM. Somatostatin inhibited glucose-induced increases in cytosolic free [Ca2+] in a dose-dependent manner (maximal inhibition was 34%). Half-maximal inhibition was observed at 10(-9) M somatostatin, which correlated well with somatostatin binding to islet cells (Kd = 2.6 X 10(-10) M). Potassium (50 mM) rapidly increased the cytosolic free [Ca2+] to 110-120 nM, and its effect was not influenced by the presence of somatostatin. Forskolin (20 microM) and dibutyryl cAMP (1 mM) rapidly increased cytosolic free Ca2+ both in the presence and absence of extracellular Ca2+. More than 80% of the overall increase in cytosolic free-Ca2+ levels could be accounted for by the mobilization of intracellular Ca2+ stores. Somatostatin effectively blocked the forskolin effect (32% inhibition) but not the dibutyryl cAMP-induced effect. Somatostatin appears to inhibit secretagogue-induced increases in cytosolic free [Ca2+] by interfering with cAMP production and probably with Ca2+ transport across the cell membrane.
D000818:Animals; D001572:Benzofurans; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology; D003600:Cytosol / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D005947:Glucose / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D013004:Somatostatin / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence
D001572:Benzofurans; D005456:Fluorescent Dyes; D005576:Colforsin; D013004:Somatostatin; D004533:Egtazic Acid; D003994:Bucladesine; D000242:Cyclic AMP; D005947:Glucose; D011188:Potassium; D002118:Calcium; D016257:Fura-2