The alpha 1-agonist phenylephrine inhibits voltage-gated Ca2(+)-channels in vascular smooth muscle cells of rabbit ear artery.

The effects of the alpha 1-agonist phenylephrine on the voltage-gated Ca2(+)-entry in vascular smooth muscle cells has been studied by measuring the agonist-induced changes of [Ca2+]i in K(+)-depolarized tissues. These changes have been estimated from the changes in fluorescence of the Ca2(+)-indicator fura-2, or have been assessed from the changes in 86Rb-efflux rate through Ca2(+)-activated K(+)-channels. Phenylephrine increases the force development in K(+)-depolarized tissues, but reduces [Ca2+]i and inhibits the 86Rb-efflux rate. However, in the presence of the Ca2(+)-entry blocker verapamil, phenylephrine increases both force development and [Ca2+]i. It is concluded that phenylephrine inhibits voltage-gated Ca2(+)-channels, and also induces an influx of calcium by activating a verapamil-insensitive pathway.