Adrenomedullin reduces intracellular calcium concentration in cultured hippocampal neurons.
The effects of adrenomedullin (ADM) on intracellular calcium concentration ([Ca(2+)](i)) were investigated in cultured hippocampal neurons. Changes in [Ca(2+)](i) were detected by laser scanning confocal microscopy using Fluo 3-AM as the calcium fluorescent probe. [Ca(2+)](i) was represented by relative fluorescent intensity. The results showed that: (1) ADM (0.01-1.0 micromol/L) decreased the resting [Ca(2+)](i) 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+)](i) induced by high K(+). (4) ADM markedly inhibited the inositol 1,4,5-trisphosphate (IP(3))-induced increase in [Ca(2+)](i), while did not influence ryanodine-evoked increase in [Ca(2+)](i). These results suggest that ADM reduces [Ca(2+)](i) 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.
Ji
Shu-Mei
SM
Department of Biomedical Engineering, Yanshan University, Qinhuangdao 066004, China.
Xue
Jian-Mei
JM
Wang
Chuan
C
Su
Su-Wen
SW
He
Rui-Rong
RR
D053607:Adrenomedullin; D000818:Animals; D000831:Animals, Newborn; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000037:antagonists & inhibitors; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010455:Peptides; D018015:Receptors, Calcitonin Gene-Related Peptide; D053607:Adrenomedullin; D015544:Inositol 1,4,5-Trisphosphate; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium