Characterization of positive inotropic effect of colforsin daropate [correction of dapropate] hydrochloride, a water-soluble forskolin derivative, in isolated adult rat cardiomyocytes.
The present study was undertaken to characterize the positive inotropic action of colforsin daropate [corrected] hydrochloride (NKH477), a novel water-soluble forskolin derivative, on isolated cardiomyocytes of adult rats. Simultaneous measurements of cellular contraction and intracellular calcium concentration ([Ca2+]i) were carried out. The effects of isoprenaline and ouabain on these parameters were also determined for comparison. The contraction and maximum [Ca2+]i of NKH477-, isoprenaline-, or ouabain-treated cells were increased concentration dependently. Peak shortening of NKH477-treated cells was positively correlated with the shortening velocity and inversely with the time to peak shortening. Maximum, but not minimum, [Ca2+]i in NKH477-treated cells was correlated with the rate of increase in [Ca2+]i and inversely with the time to maximum [Ca2+]i. Similar results were obtained with isoprenaline. In contrast, ouabain increased both maximum and minimum [Ca2+]i. Treatment with either NKH477 or isoprenaline increased cellular cAMP content, but treatment with ouabain did not. These results suggest that the positive inotropic action of NKH477 is associated with an increase in [Ca2+]i and acceleration of its kinetics.
Miyake
R
R
Department of Pharmacology, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
Yoshida
H
H
Tanonaka
K
K
Miyamoto
Y
Y
Hayashi
H
H
Kajiwara
H
H
Takeo
S
S
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D005576:Colforsin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002316:Cardiotonic Agents; D005576:Colforsin; D010042:Ouabain; D000242:Cyclic AMP; D007545:Isoproterenol; D002118:Calcium