Production of cAMP by adrenomedullin in human oligodendroglial cell line KG1C: comparison with calcitonin gene-related peptide and amylin.
The actions and the presence of adrenomedullin (AM) were investigated in cultured human oligodendroglial cell line KG1C. AM and AM mRNA were detected in KG1C cells by immunohistochemistry and RT-PCR. mRNAs for calcitonin receptor-like receptor (CRLR) and receptor-activity-modifying proteins (RAMPs) 1, 2 and 3 but not for calcitonin receptors were detected in the cells, while mRNAs for CRLR, calcitonin receptors and all RAMPs were detected in the human cerebellum. Application of AM resulted in time- and concentration-dependent increases in the cAMP level of KG1C cells. Calcitonin gene-related peptide (CGRP) and amylin, peptides structurally related to AM, also increased cAMP. The potencies for the cAMP production of the three peptides were CGRP > or =AM >> amylin with EC(50) of 8, 18, 90 nM, respectively. The responses induced by AM were strongly inhibited by the CGRP(1) receptor antagonist human CGRP(8-37), and inhibited also by the AM receptor antagonist human AM(22-52). In contrast, the responses induced by CGRP or amylin were inhibited only by CGRP(8-37) and not by AM(22-52). The responses induced by all three peptides were unaffected by the amylin receptor antagonist human amylin(8-37). The CGRP(2) receptor agonist human [Cys(Acm)(2,7)]CGRP significantly increased the cAMP level but the increase was smaller than that caused by CGRP. This increase in cAMP was unaffected by CGRP(8-37), AM(22-52) or by amylin(8-37). These results suggest that in KG1C cells, AM increases cAMP through AM and CGRP(1) receptors, whereas CGRP does so through CGRP(1) and CGRP(2) receptors, and amylin exerts its effects through CGRP(1) receptors. Collectively, these findings imply that AM released from oligodendroglial cells may play a role in the regulation of oligodendrocytes via autocrine/paracrine through AM receptors and CGRP(1) receptors.
Uezono
Y
Y
Department of Pharmacology, Miyazaki Medical College, 5200 Kihara, 889-1692, Kiyotake, Japan. uezonoy@alpha.med.nagasaki-u.ac.jp
Nakamura
E
E
Ueda
Y
Y
Shibuya
I
I
Ueta
Y
Y
Yokoo
H
H
Yanagita
T
T
Toyohira
Y
Y
Kobayashi
H
H
Yanagihara
N
N
Wada
A
A
D000313:Adrenal Medulla / Q000166:cytology; D053607:Adrenomedullin; D000682:Amyloid / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D019898:Autocrine Communication; D001932:Brain Neoplasms / Q000473:pathology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology / Q000502:physiology*; D058286:Calcitonin Receptor-Like Protein; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005910:Glioma / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D058228:Islet Amyloid Polypeptide; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009836:Oligodendroglia / Q000378:metabolism*; D019899:Paracrine Communication; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology*; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin / Q000096:biosynthesis / Q000235:genetics; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000187:drug effects; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015290:Second Messenger Systems / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000682:Amyloid; C545578:CALCRL protein, human; D058286:Calcitonin Receptor-Like Protein; D047908:Intracellular Signaling Peptides and Proteins; D058228:Islet Amyloid Polypeptide; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D010455:Peptides; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin; D018015:Receptors, Calcitonin Gene-Related Peptide; D058287:Receptors, Islet Amyloid Polypeptide; D018000:Receptors, Peptide; C104782:adrenomedullin (22-52); C109255:amylin (8-37); C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; D000242:Cyclic AMP; D015740:Calcitonin Gene-Related Peptide