Corticotropin-releasing factor modulation of Ca2+ influx in rat pancreatic beta-cells.
The effects of corticotropin-releasing factor (CRF) on the intracellular concentration of Ca2+ were studied in isolated single beta-cells of the rat islet. Immunohistochemical staining using CRF-receptor antibodies revealed the presence of both type 1 (CRF-R1) and type 2 (CRF-R2) receptors for CRF in the majority of islet cells. CRF (2 nmol/l) increased cytosolic Ca2+ concentration under 2.8 mmol/l glucose, dependent upon extracellular Ca2+. CRF caused depolarization of the cell membrane, which was followed by action potentials under 2.8 mmol/l glucose. The dose-response relationships of CRF-induced depolarization in the presence of 1 micromol/l nifedipine produced a bell-shaped curve, showing the peak response at 2 nmol/l. In the whole-cell patch-clamp recording, CRF enhanced Ca2+ currents through L-type Ca2+ channels in a dose-dependent manner similar to that for depolarization. In cells pretreated with Rp-deastereomer of adenosine cyclic 3',5'-phosphorothiolate (100 micromol/l), neither depolarization nor an increase in the Ca2+ current was caused by CRF at concentrations <2 nmol/l. In these cells, CRF at 20 nmol/l reduced the Ca2+ current. These results suggest that in single beta-cells of rat islets, CRF, through its own receptor, potentiates Ca2+ influx through the L-type Ca2+ channel by activation of the cAMP/protein kinase A signaling pathway. CRF at a high concentration also shows an inhibitory effect on the Ca2+ current through an unknown signaling pathway.
Kanno
T
T
Department of Physiology, Hirosaki University School of Medicine, Japan. tkanno@cc.hirosaki-u.ac.jp
Suga
S
S
Nakano
K
K
Kamimura
N
N
Wakui
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
D003346:Corticotropin-Releasing Hormone; D002118:Calcium