Corticotropin-releasing factor modulation of Ca2+ influx in rat pancreaticbeta-cells

The effects of corticohopin-releasing-factor (CRF) on the intracellular con centration of Ca were studied in isolated single beta-cells of the rat isle t, Immunohistochemical staining using CRF-receptor antibodies revealed the presence of both type 1 (CRF-R1) and type 2 (CRF-RB) receptors for CRF in t he majority of islet cells. CRF (2 nmol/l) increased cytosolic Ca2+ concent ration under 2.8 mmol/l glucose, dependent upon extracellular Ca2+, CRF cau sed depolarization of the cell membrane, which was followed by action poten tials under 2.8 mmol/l glucose. The dose-response relationships of CRF-indu ced depolarization in the presence of 1 mu mol/l nifedipine produced a bell -shaped curve, showing the peak response at 2 nmol/l, In the whole-cell pat ch-clamp recording, CRF enhanced Ca2+ currents through L-type Ca2+ channels in a dose-dependent manner similar to that for depolarization. In cells pr etreated with Rp-deastereomer of adenosine cyclic 3',5'-phosphorothiolate ( 100 mu mol/l), neither depolarization nor an increase in the Ca2+ current w as caused by CRF at concentrations <2 nmol/l, In these cells, CRF at 20 nmo l/l reduced the Ca2+ current. These results suggest that in single beta-cel ls of rat islets, CRF, through its own receptor, potentiates Ca2+ influx th rough the L-type Ca2+ channel by activation of the cAMP/protein kinase A si gnaling pathway. CRF at a high concentration also shows an inhibitory effec t on the Ca2+ current through an unknown signaling pathway.