Modulation of Ca2+ influx by corticotropin-releasing factor (CRF) family of peptides via CRF receptors in rat pancreatic beta-cells.
The actions of the corticotropin-releasing factor (CRF) family of peptides are mediated by the seven transmembrane-domain G-protein-coupled receptors, the CRF receptors type 1 (CRF1 receptor) and type 2 (CRF2 receptor). In a previous study, we reported that CRF, an endogenous ligand for CRF1 receptor, modulated Ca2+ influx in rat pancreatic beta-cells. In addition to CRF, other additional members of the family, urocortins, have been identified in mammals. Urocortin 1 (UCN 1), a peptide of the CRF family, binds both CRF1 receptor and CRF2 receptor with equal affinities. Urocortin 3 (UCN 3), a highly selective ligand for CRF2 receptor with little affinity for CRF1 receptor, has been shown in rat pancreatic beta-cells. The present study focused on the effects of the CRF family peptides on intracellular Ca2+ ([Ca2+]i) concentration via CRF receptors in rat pancreatic beta-cells. Microfluorimetric experiments showed that CRF (0.2 nM) and UCN 1 (0.2 nM) elevated [Ca2+]i levels. Both CRF and UCN 1 effects were attenuated by astressin, a non-selective CRF receptor antagonist. Antisauvagine-30, a selective CRF2 receptor antagonist, appeared to enhance the UCN 1 effect on the elevation of [Ca2+]i. The CRF effect on the elevation of [Ca2+]i was inhibited by the addition of UCN 3. Taken together, the activation of CRF2 receptor antagonizes the CRF1 receptor-stimulated Ca2+ influx.
Kageyama
Kazunori
K
Department of Endocrinology, Metabolism and Infectious Diseases Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori 036-8562, Japan. kkageyama@hkg.odn.ne.jp
Kimura
Ryoichi
R
Suga
Sechiko
S
Ogawa
Yoshiji
Y
Suda
Toshihiro
T
Wakui
Makoto
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008024:Ligands; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism; D054832:Urocortins
C101531:CRF receptor type 2; D008024:Ligands; D010446:Peptide Fragments; D010455:Peptides; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C104416:astressin; D003346:Corticotropin-Releasing Hormone; D002118:Calcium