Effects of AMP579 and adenosine on L-type Ca~(2+)current in isolated rat ventricular myocytes

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:longerken
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Aim:To compare the effects of AMP579 and adenosine on L-type Ca~(2+)current(I_(Ca-L))in rat ventricular myocytes and explore the mechanism by which AMP579acts on I_(Ca_L).Methods:I_(Ca_L)was recorded by patch-clamp technique in whole-cellconfiguration.Results:Adenosine(10nmol/L to 50μmol/L)showed no effect onbasal I_(Ca_L),but it inhibited the I_(Ca_L)induced by isoproterenol 10 nmol/L in a concen-tration-dependent manner with the IC_(50)of 13.06 μmol/L.Similar to adenosine,AMP579 also showed an inhibitory effect on the I_(Ca_L)induced by isoproterenol.AMP579 and adenosine(both in 10 μmol/L)suppressed isoproterenol-inducedI_(Ca_L)by 11.1% and 5.2%, respectively.In addition,AMP579 had a direct inhibitoryeffect on basal I_(Ca_L)in a concentration-dependent manner with IC_(50)(1.17 μmol/L).PD 116948(30μmol/L),an adenosine A_1 receptor blocker,showed no action on theinhibitory effect of AMP579 on basal I_(Ca_L).However,GF109203X(0.4μmol/L),aspecial protein kinase C(PKC)blocker,could abolish the inhibitory effect of AMP579on basal I__(Ca_L).So the inhibitory effect of AMP579 on basal I_(Ca_L)was inducedthrough activating PKC,but not linked to adenosine A_1 receptor.Conclusion:AMP579 shows a stronger inhibitory effect than adenosine on the I_(Ca_L)inducedby isoproterenol.AMP579 also has a strong inhibitory effect on basal I_(Ca_L)in ratventricular myocytes.Activation of PKC is involved in the inhibitory effect ofAMP579 on basal I_(Ca_L)at downstream-mechanism. Aim: To compare the effects of AMP579 and adenosine on L-type Ca ~ (2+) current (I_ (Ca-L)) in rat ventricular myocytes and explore the mechanism by which AMP579acts on I_ (Ca_L). Methods: Ca_L) was recorded by patch-clamp technique in whole-cell configuration.Results: Adenosine (10nmol / L to 50μmol / L) showed no effect onbasal I_ (Ca_L), but it inhibited the I_ (Ca_L) induced by isoproterenol 10 nmol / L in a concen-tration-dependent manner with the IC 50 (50) of 13.06 μmol / L.Similar to adenosine, AMP 579 also showed an inhibitory effect on I_ (Ca_L) induced by isoproterenol.AMP579 and adenosine (both in 10 μmol / 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 IC 50 116948 (30μmol / L), an adenosine A_1 receptor blocker, showed no action on the inhibitory effect of AMP579 on basal I_ (Ca_L) .However, GF109203X (0.4μmol / L), aspecial protein kinase C (PKC) abolish the inhibitory effect of AMP579on basal I__ (Ca_L) .So the inhibitory effect of AMP579 on basal I_ (Ca_L) was inducedthroughactivating PKC, but not linked to adenosine A_1 receptor.Conclusion: AMP579 shows a stronger inhibitory effect than adenosine on the I_ (Ca_L) inducedby isoproterenol.AMP579 also has a strong inhibitory effect on basal I_ (Ca_L) in ratventricular myocytes. Activation of PKC is involved in the inhibitory effect of AMP579 on basal I_ (Ca_L) at downstream-mechanism.
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