Urocortin has cell-proliferative effects on cardiac non-myocytes.
Urocortin (Ucn) is a member of the corticotropin-releasing hormone (CRH)-related peptides that has been reported to have cardiac inotropic and hypertrophic effects. In addition, Ucn mRNA was expressed in cardiac myocytes (MCs) and Ucn was suggested to have cardioprotective effects. Recently, it was reported that Ucn mRNA was expressed in cardiac non-myocytes (NMCs). Based on these facts, Ucn is assumed to affect not only MCs but also NMCs in an autocrine fashion. The present study was designed to elucidate a pathophysiological role of Ucn on NMCs. NMCs were prepared by the discontinuous Percoll gradient and adhesion method. Ucn increased [(3)H]-thymidine uptake into NMCs. Ucn also enhanced endothelin-1-induced increase of [(3)H]-thymidine uptake into NMCs. Effects of Ucn on [(3)H]-thymidine uptake into NMCs were significantly abolished by the protein kinase A inhibitor, H89 (10(-5) M), but not by a competitive antagonist of CRH receptors, astressin (10(-5) M). Ucn also increased intracellular cAMP accumulation more potently than CRH on a molar basis. Finally, both MCs and NMCs also secreted Ucn. Together with the recent findings, at least in NMCs, these data suggest that Ucn could exert its own actions via the cAMP signaling pathway, but not through known CRH type 2 receptors, in an autocrine fashion. In conclusion, the present study indicated that Ucn was secreted not only from MCs but also from NMCs and that the primary source of Ucn acting on heart was the heart itself. On the other hand, Ucn could proliferate NMCs as well as MCs, suggesting that Ucn could be involved in cardiac hypertrophy and fibrosis, i.e., cardiac remodeling, in spite of its putative cardioprotective actions.
Ikeda
Keiichi
K
Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8, Nishishinbashi, Minatoku, Tokyo 105-8461, Japan.
Tojo
Katsuyoshi
K
Oki
Yutaka
Y
Nakao
Kazuwa
K
D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D006321:Heart / Q000187:drug effects*; D007930:Leucine / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000166:cytology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D013936:Thymidine / Q000378:metabolism; D054832:Urocortins
D018696:Neuroprotective Agents; D010446:Peptide Fragments; D054832:Urocortins; C104416:astressin; D005576:Colforsin; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D007930:Leucine; D013936:Thymidine