9 páginas, 7 figuras.Glucose homeostasis in blood is mainly maintained by insulin released from β-cells and glucagon released from α-cells, both integrated within the pancreatic islet of Langerhans. The secretory processes in both types of cells are triggered by a rise in intracellular calcium concentration ([Ca2+]i). In this study, rapid effects of the natural hormone E2 on [Ca2+]i were studied in both types of cells within intact islets using laser scanning confocal microscopy. α- And β-cells showed opposite [Ca2+]i responses when stimulated with physiological concentrations of 17β-E2. Although the estrogen produced an increase in the frequency of glucose-induced [Ca2+]i oscillations in insulin-releasing β-cells, it prevented the low glucose-induced [Ca2+]i oscillations in glucagon-releasing α-cells. The effects of 17β-E2 on α-cells were mimicked by the cGMP permeable analog 8bromo-cGMP and blocked by the cGMP-dependent protein kinase (PKG) inhibitor KT5823. Evidence indicated that these were membrane actions mediated by a nonclassical ER. Both effects were rapid in onset and were reproduced by 17β-E2 linked to horseradish peroxidase, a cell-impermeable molecule. Furthermore, these actions were not blocked by the specific ER blocker ICI 182,780. Competition studies performed with 17β-E2 linked to horseradish peroxidase binding in α-cells supported the idea that the membrane receptor involved is neither ERα nor ERβ. Additionally, the binding site was shared by the neurotransmitters epinephrine, norepinephrine, and dopamine and had the same pharmacological profile as the receptor previously described for β-cells. Therefore, rapid estrogen actions in islet cells are initiated by a nonclassical estrogen membrane receptor.This work was supported by Grants from European Union- \ud Comisión Interministerial de Ciencia y Tecnología (IFD97- \ud 1064-103-02) and Fundación Navarro Trípodi. A.B.R. is a \ud recipient of a research scholarship from de Ministerio de \ud Educación, Cultura y Deporte.Peer reviewe