Abstract
Aim:
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 umol/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 IC50 of 13.06 umol/L. Similar to adenosine, AMP579 also showed an inhibitory effect on the I Ca-L induced by isoproterenol. AMP579 and adenosine (both in 10 umol/L) suppressed isoproterenol-induced I Ca-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 μmol/L). PD116948 (30 μmol/L), an adenosine A1 receptor blocker, showed no action on the inhibitory effect of AMP579 on basal I Ca-L. However, GF109203X (0.4 μmol/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.
Conclusion:
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.
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Wang, X., Wu, Bw. & Wu, Dm. Effects of AMP579 and adenosine on L-type Ca2+ current in isolated rat ventricular myocytes. Acta Pharmacol Sin 26, 559–562 (2005). https://doi.org/10.1111/j.1745-7254.2005.00107.x
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DOI: https://doi.org/10.1111/j.1745-7254.2005.00107.x
