Adrenomedullin reduces intracellular calcium concentration in cultured hippocampal neurons

The effects of adrenomedullin (ADM) on intracellular calcium concentration ([Ca2+]i) were investigated in cultured hippoc-ampal neurons. Changes in [Ca2+]i were detected by laser scanning confocal microscopy using Fluo 3-AM as the calcium fluorescentprobe. [Ca2+]i was represented by relative fluorescent intensity. The results showed that: (1) ADM (0.01~1.0 μmol/L) decreased theresting [Ca2+]i in a concentration-dependent manner. (2) Calcitonin gene-related peptide receptor antagonist CGRP8-37 significantlyinhibited the effects of ADM. (3) ADM significantly reduced the increase in [Ca2+]i induced by high K+. (4) ADM markedly inhibitedthe inositol 1,4,5-trisphosphate (IP3)-induced increase in [Ca2+]i, while did not influence ryanodine-evoked increase in [Ca2+]i. Theseresults suggest that ADM reduces [Ca2+]i in cultured hippocampal neurons through suppressing Ca2+ release from IP3-sensitive stores.Although ADM does not alter resting Ca2+ influx, it significantly suppresses Ca2+ influx activated by high K+. These effects may bepartly mediated by CGRP receptors. ADM in the CNS may act as a cytoprotective factor in ischemic/hypoxic conditions.