title: Cytosolic calcium oscillations induced by hepatocyte growth factor (HGF) in single fura-2-loaded cultured hepatocytes: effects of extracellular calcium and protein kinase C.
abstract: Hepatocyte growth factor (HGF) induced the periodic fluctuations of cytosolic calcium concentration ([Ca2+]i) in primary cultured rat hepatocytes, which were dependent on extracellular calcium. The HGF-induced [Ca2+]i oscillations were suppressed by the pretreatment with phorbol 12-myristate 13-acetate (PMA). Administration of PMA during oscillations also caused their blockade, but the subsequent addition of protein kinase C (PKC) inhibitor H-7 reversed the inhibitory effects of PMA, thereby resulting in the resumption of the oscillatory responses. Moreover, the prior exposure to H-7 caused apparent increases in [Ca2+]i spike peaks elicited by HGF. These results suggest a negative modulation via PKC in HGF-induced repetitive [Ca2+]i transients. The absence of HGF-induced oscillations after the thapsigargin treatment indicates that the agonist-sensitive intracellular Ca2+ pool plays a crucial role in the [Ca2+] oscillations.
authors.affiliation: Second Department of Surgery, Gifu University School of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Osada
authors.forename: S
authors.initials: S
authors.lastname: Saji
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: Y
authors.initials: Y
authors.lastname: Nozawa
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001663:Bilirubin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D016257:Fura-2; D007546:Isoquinolines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D012709:Serum Albumin / Q000494:pharmacology*; D000075462:Serum Albumin, Human; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
chemical_list: D007546:Isoquinolines; D010879:Piperazines; D012709:Serum Albumin; D013729:Terpenes; C053498:albumin-bilirubin complex; D004533:Egtazic Acid; D019284:Thapsigargin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D001663:Bilirubin; D002118:Calcium; D016257:Fura-2; D000075462:Serum Albumin, Human