Adrenomedullin increases intracellular Ca2+ and inositol 1,4,5-trisphosphate in human oligodendroglial cell line KG-1C.
The effects of adrenomedullin (AM), a hypotensive peptide, were investigated in cultured human oligodendroglial cell line KG-1C. Human AM increased the intracellular Ca2+ concentration ([Ca2+]i) at concentrations greater than 10(-7) M. Human calcitonin gene-related peptide (CGRP), a peptide structurally related to AM, also increased [Ca2+]i with a potency similar to that of AM. AM increased [Ca2+]i in the absence of extracellular Ca2+. Further, AM increased inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) level in a concentration-dependent manner similar to that of AM-induced [Ca2+]i, suggesting that AM-induced elevation of [Ca2+]i is due to Ca2+ release from Ins(1,4,5)P3-sensitive stores. AM (10(-9) to 10(-6) M) increased cAMP in a concentration-dependent manner. Forskolin also increased cAMP, but did not mimic the [Ca2+]i-raising effect of AM. These findings suggest that functional AM receptors are present in oligodendroglial KG-1C cells and that AM increases [Ca2+]i through a mechanism independent of cAMP.
Uezono
Y
Y
Department of Pharmacology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu 807-8555, Japan. uezonoy@med.uoeh-u.ac.jp
Shibuya
I
I
Ueda
Y
Y
Tanaka
K
K
Oishi
Y
Y
Yanagihara
N
N
Ueno
S
S
Toyohira
Y
Y
Nakamura
T
T
Yamashita
H
H
Izumi
F
F
D053607:Adrenomedullin; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism*; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D010455:Peptides; D053607:Adrenomedullin; D005576:Colforsin; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium