title: Effects of AMP579 and adenosine on L-type Ca2+ current in isolated rat ventricular myocytes.
abstract: OBJECTIVE
  To compare the effects of AMP579 and adenosine on L-type Ca2+ current (I(Ca-L)) in rat ventricular myocytes and explore the mechanism by which AMP579 acts on I(Ca-L).
  
  
  METHODS
  I(Ca-L) was recorded by patch-clamp technique in whole-cell configuration.
  
  
  RESULTS
  Adenosine (10 nmol/L to 50 micromol/L) showed no effect on basal I(Ca-L), but it inhibited the I(Ca-L) induced by isoproterenol 10 nmol/L in a concentration-dependent manner with the IC(50) of 13.06 micromol/L. Similar to adenosine, AMP579 also showed an inhibitory effect on the I(Ca-L) induced by isoproterenol. AMP579 and adenosine (both in 10 micromol/L) suppressed isoproterenol-induced ICa-L by 11.1% and 5.2%, respectively. In addition, AMP579 had a direct inhibitory effect on basal I(Ca-L) in a concentration-dependent manner with IC50 (1.17 micromol/L). PD116948 (30 micromol/L), an adenosine A1 receptor blocker, showed no action on the inhibitory effect of AMP579 on basal I(Ca-L). However, GF109203X (0.4 micromol/L), a special protein kinase C (PKC) blocker, could abolish the inhibitory effect of AMP579 on basal I(Ca-L). So the inhibitory effect of AMP579 on basal I(Ca-L) was induced through activating PKC, but not linked to adenosine A1 receptor.
  
  
  CONCLUSIONS
  AMP579 shows a stronger inhibitory effect than adenosine on the I(Ca-L) induced by isoproterenol. AMP579 also has a strong inhibitory effect on basal I(Ca-L) in rat ventricular myocytes. Activation of PKC is involved in the inhibitory effect of AMP579 on basal I(Ca-L) at downstream-mechanism.
authors.affiliation: Department of Physiology, Shanxi Medical University, Taiyuan 030001, China. Wxiong@public.ty.sx.cn
authors.forename: Xiong
authors.initials: X
authors.lastname: Wang
authors.forename: Bo-wei
authors.initials: BW
authors.lastname: Wu
authors.forename: Dong-mei
authors.initials: DM
authors.lastname: Wu
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000166:cytology; D007093:Imidazoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014970:Xanthines / Q000494:pharmacology
chemical_list: C113971:4-(7-((2-3-chloro-2-thienyl)-1-methyl-propylamino)-3H-imidazo(4,5-b)pyridyl-3-yl)cyclopentane carboxamide; D058916:Adenosine A1 Receptor Antagonists; D020746:Calcium Channels, L-Type; D002316:Cardiotonic Agents; D007093:Imidazoles; D007211:Indoles; D008301:Maleimides; D011725:Pyridines; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine; D011493:Protein Kinase C; D000241:Adenosine; C070515:bisindolylmaleimide I