Adrenomedullin reduces intracellular calcium concentration in cultured hippocampal neurons.

The effects of adrenomedullin (ADM) on intracellular calcium concentration (Ca(2+)) were investigated in cultured hippocampal neurons. Changes in Ca(2+) were detected by laser scanning confocal microscopy using Fluo 3-AM as the calcium fluorescent probe. Ca(2+) was represented by relative fluorescent intensity. The results showed that: (1) ADM (0.01-1.0 micromol/L) decreased the resting Ca(2+) in a concentration-dependent manner. (2) Calcitonin gene-related peptide receptor antagonist CGRP(8-37) significantly inhibited the effects of ADM. (3) ADM significantly reduced the increase in Ca(2+) induced by high K(+). (4) ADM markedly inhibited the inositol 1,4,5-trisphosphate (IP(3))-induced increase in Ca(2+), while did not influence ryanodine-evoked increase in Ca(2+). These results suggest that ADM reduces Ca(2+) in cultured hippocampal neurons through suppressing Ca(2+) release from IP(3)-sensitive stores. Although ADM does not alter resting Ca(2+) influx, it significantly suppresses Ca(2+) influx activated by high K(+). These effects may be partly mediated by CGRP receptors. ADM in the CNS may act as a cytoprotective factor in ischemic/hypoxic conditions.