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  • Title: Reserpine has a direct action as a calcium antagonist on mammalian smooth muscle cells.
    Author: Casteels R, Login IS.
    Journal: J Physiol; 1983 Jul; 340():403-14. PubMed ID: 6310099.
    Abstract:
    The effects of reserpine on excitation-contraction coupling and 45Ca exchange of smooth muscle cells of the rabbit ear artery and the guinea-pig taenia coli have been studied. Reserpine inhibited the spontaneous mechanical activity of the taenia coli and the force development induced by 59 mM-external K or 10(-5) M-carbachol. In the ear artery reserpine blocked the K-induced contraction but its effect on the contraction elicited by noradrenaline was smaller. At 0.2 mM-Ca, the inhibition of the tonic component of the noradrenaline-induced contraction was more pronounced than that of the phasic component. This reserpine action was fully reversible for the noradrenaline stimulus in the ear artery but less so for K-induced contractions. The inhibitory action on contractions induced in taenia coli by K-rich solution and by carbachol was even less reversible. The analysis of the effect of reserpine on the 45Ca exchange in the ear artery has revealed that it inhibits the increase of the fractional loss induced by K depolarization, but that it does not exert a significant effect on the increased fractional loss induced by 10(-5) M-noradrenaline. Reserpine slows down the filling with 45Ca of the agonist-sensitive store without affecting the steady-state amount of Ca taken up by the store. A study of the degree of filling of the store by measuring the force development and the 45Ca release elicited by noradrenaline in Ca-free medium, reveals that the force development after loading in a reserpine-containing medium remains less than the control, although the same amount of Ca is released from the store. It was shown by using tetrabenazine that the inhibitory action of reserpine on the Ca exchange and the force development is not due to an interaction of reserpine with the receptor molecules that are responsible for its depleting action on aminergic granules. These results strongly suggest that reserpine exerts a Ca antagonistic action on smooth muscle whereby it blocks the potential-dependent channels. However, reserpine also affects the receptor-operated channels to some extent and in addition at a high concentration it seems to exert an unspecific inhibitory action on the contractile system.
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