Modulation of Ca 2+ influx by corticotropin-releasing factor (CRF) family of peptides via CRF receptors in rat pancreatic β-cells

Abstract

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 (CRF 1 receptor) and type 2 (CRF 2 receptor). In a previous study, we reported that CRF, an endogenous ligand for CRF 1 receptor, modulated Ca 2+ influx in rat pancreatic β-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 CRF 1 receptor and CRF 2 receptor with equal affinities. Urocortin 3 (UCN 3), a highly selective ligand for CRF 2 receptor with little affinity for CRF 1 receptor, has been shown in rat pancreatic β-cells. The present study focused on the effects of the CRF family peptides on intracellular Ca 2+ ([Ca 2+] i) concentration via CRF receptors in rat pancreatic β-cells. Microfluorimetric experiments showed that CRF (0.2 nM) and UCN 1 (0.2 nM) elevated [Ca 2+] i levels. Both CRF and UCN 1 effects were attenuated by astressin, a non-selective CRF receptor antagonist. Antisauvagine-30, a selective CRF 2 receptor antagonist, appeared to enhance the UCN 1 effect on the elevation of [Ca 2+] i. The CRF effect on the elevation of [Ca 2+] i was inhibited by the addition of UCN 3. Taken together, the activation of CRF 2 receptor antagonizes the CRF 1 receptor-stimulated Ca 2+ influx.