Blockade of L-type calcium channel in myocardium and calcium-induced contractions of vascular smooth muscle by CPU 86017
Abstract
AIM:
To assess the blockade by CPU 86017 on the L-type calcium channels in the myocardium and on the Ca(2+)-related contractions of vascular smooth muscle.
METHODS:
The whole-cell patch-clamp was applied to investigate the blocking effect of CPU 86017 on the L-type calcium current in isolated guinea pig myocytes and contractions by KCl or phenylephrine (Phe) of the isolated rat tail arteries were measured.
RESULTS:
Suppression of the L-type current of the isolated myocytes by CPU 86017 was moderate, in time- and concentration-dependent manner and with no influence on the activation and inactivation curves. The IC(50) was 11.5 micromol/L. Suppressive effect of CPU 86017 on vaso-contractions induced by KCl 100 mmol/L, phenylephrine 1 micromol/L in KH solution (phase 1), Ca(2+) free KH solution ( phase 2), and by addition of CaCl(2) into Ca(2+)-free KH solution (phase 3) were observed. The IC(50) to suppress vaso-contractions by calcium entry via the receptor operated channel (ROC) and voltage-dependent channel (VDC) was 0.324 micromol/L and 16.3 micromol/L, respectively. The relative potency of CPU 86017 to suppress vascular tone by Ca(2+) entry through ROC and VDC is 1/187 of prazosin and 1/37 of verapamil, respectively.
CONCLUSION:
The blocking effects of CPU 86017 on the L-type calcium channel of myocardium and vessel are moderate and non-selective. CPU 86017 is approximately 50 times more potent in inhibiting ROC than VDC.
Keywords:
To assess the blockade by CPU 86017 on the L-type calcium channels in the myocardium and on the Ca(2+)-related contractions of vascular smooth muscle.
METHODS:
The whole-cell patch-clamp was applied to investigate the blocking effect of CPU 86017 on the L-type calcium current in isolated guinea pig myocytes and contractions by KCl or phenylephrine (Phe) of the isolated rat tail arteries were measured.
RESULTS:
Suppression of the L-type current of the isolated myocytes by CPU 86017 was moderate, in time- and concentration-dependent manner and with no influence on the activation and inactivation curves. The IC(50) was 11.5 micromol/L. Suppressive effect of CPU 86017 on vaso-contractions induced by KCl 100 mmol/L, phenylephrine 1 micromol/L in KH solution (phase 1), Ca(2+) free KH solution ( phase 2), and by addition of CaCl(2) into Ca(2+)-free KH solution (phase 3) were observed. The IC(50) to suppress vaso-contractions by calcium entry via the receptor operated channel (ROC) and voltage-dependent channel (VDC) was 0.324 micromol/L and 16.3 micromol/L, respectively. The relative potency of CPU 86017 to suppress vascular tone by Ca(2+) entry through ROC and VDC is 1/187 of prazosin and 1/37 of verapamil, respectively.
CONCLUSION:
The blocking effects of CPU 86017 on the L-type calcium channel of myocardium and vessel are moderate and non-selective. CPU 86017 is approximately 50 times more potent in inhibiting ROC than VDC.