PMID- 9794468 OWN - NLM STAT- MEDLINE DCOM- 19981106 LR - 20131121 IS - 0013-7227 (Print) IS - 0013-7227 (Linking) VI - 139 IP - 11 DP - 1998 Nov TI - Production and secretion of adrenomedullin in cultured rat cardiac myocytes and nonmyocytes: stimulation by interleukin-1beta and tumor necrosis factor-alpha. PG - 4576-80 AB - The present study investigated the secretion level and gene expression of adrenomedullin (AM), a novel vasorelaxant peptide, in cultured neonatal rat cardiac myocytes and nonmyocytes, and the effects of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF alpha) on its production and secretion in these cells. Under serum-free conditions, both myocytes and nonmyocytes secreted immunoreactive (ir-) AM into the culture medium in a time-dependent manner. The secretion rates of ir-AM from myocytes and nonmyocytes per 10(5) cells were almost equivalent. The expression of AM messenger RNA was also observed in cultured myocytes and nonmyocytes. The peptide secretion and messenger RNA level of AM in cardiac myocytes were increased after stimulation with IL-1beta. In nonmyocytes, IL-1beta and TNF alpha remarkably augmented both the release of ir-AM into the medium and AM gene expression after 24 and 48 h of incubation. These observations indicate that cardiac ventricular cells (i.e. myocytes and nonmyocytes) actively produce AM and also suggest that cytokines such as IL-1beta and TNF alpha regulate the gene expression and secretion of this peptide in the ventricles. On the basis of these results and the findings that IL-1beta and TNF alpha are involved in heart failure and cardiac hypertrophy, AM may play a role as an autocrine/paracrine modulator in some cardiac disorders. FAU - Horio, T AU - Horio T AD - Department of Medicine, National Cardiovascular Center, Suita, Osaka, Japan. FAU - Nishikimi, T AU - Nishikimi T FAU - Yoshihara, F AU - Yoshihara F FAU - Nagaya, N AU - Nagaya N FAU - Matsuo, H AU - Matsuo H FAU - Takishita, S AU - Takishita S FAU - Kangawa, K AU - Kangawa K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Endocrinology JT - Endocrinology JID - 0375040 RN - 0 (Culture Media) RN - 0 (Endothelin-1) RN - 0 (Interleukin-1) RN - 0 (Peptides) RN - 0 (RNA, Messenger) RN - 0 (Tumor Necrosis Factor-alpha) RN - 11128-99-7 (Angiotensin II) RN - 148498-78-6 (Adrenomedullin) RN - 1WS297W6MV (Phenylephrine) RN - 85637-73-6 (Atrial Natriuretic Factor) SB - IM MH - Adrenomedullin MH - Angiotensin II/pharmacology MH - Animals MH - Atrial Natriuretic Factor/biosynthesis MH - Blotting, Northern MH - Cells, Cultured MH - Culture Media MH - Endothelin-1/pharmacology MH - Heart/drug effects MH - Interleukin-1/*pharmacology MH - Myocardium/cytology/*metabolism MH - Peptides/*metabolism MH - Phenylephrine/pharmacology MH - RNA, Messenger/biosynthesis MH - Rats MH - Rats, Wistar MH - Stimulation, Chemical MH - Tumor Necrosis Factor-alpha/*pharmacology EDAT- 1998/10/30 00:00 MHDA- 1998/10/30 00:01 CRDT- 1998/10/30 00:00 PHST- 1998/10/30 00:00 [pubmed] PHST- 1998/10/30 00:01 [medline] PHST- 1998/10/30 00:00 [entrez] AID - 10.1210/endo.139.11.6306 [doi] PST - ppublish SO - Endocrinology. 1998 Nov;139(11):4576-80. doi: 10.1210/endo.139.11.6306.