Mechanisms of Inhibitory Action of Phenylephrine in Guinea-Pig Taenia Coli

Abstract

Abstract-The effect of phenylephrine, an a-agonist, on the Ca movements and the influence of removal of external Na+ on the relaxant activity of phenylephrine were examined in the taenia coil of guinea pigs. Phenylephrine (10-7-10-5 M) caused dose-dependent relaxation of the taenia coli contracted by 20 mM KCI in Locke-Ringer solution. Phenylephrine (10-5 M) suppressed the spike discharges of the taenia coil evoked by 20 mM KCI without affecting the membrane potential, and this was accompanied by the muscle relaxation. Phenylephrine also inhibited the cellular 45Ca-uptake in the taenia coil, but had no discernible effect on the 45Ca efflux from the smooth muscle. These effects of phenylephrine were not observed in a Na-free solution or in the highly depolarized smooth muscle. These findings suggest that the inhibition of Ca-influx in the taenia coil may be involved in the phenylephrine-induced relaxation in the partly depolarized tissue. Reasons for reduction of phenylephrine action encountered under the Na-free condition were also discussed.cytoplasmic Ca2+ concentration (10, 11) and modifies the activity of smooth muscle relaxants (4, 5, 12, 13). Bulbring and Tomita (14) found that the a-adrenoceptor mediated relaxing action of adrenaline was reduced when Na+ was removed from the bathing fluid, leading them to postulate that the reduction in the adrenaline effect was related to the changes in the Ca distribution within the smooth muscle cells, which had been caused by the removal of external Nat However, den Hertog (8) and Watanabe (15) claimed that external Na+ is unnecessary for the a-adrenaline action. Thus, it is of interest to examine how the relaxant action of a agonists will be influenced when the Na+ gradient across the cell membrane is changed.In the present study, the authors aimed to explore the mechanisms of the relaxation induced by the activation of a-adrenoceptor through examining the effect of phenyle phrine on the Ca movements and to elucidate the role of external Na+ in the phenylephrine induced relaxation in the taenia coll.

Effects of sucrose- or Tris-substitution for Na+ on responses to D 600, papaverine and KCN in the K+-depolarized taenia coli of guinea pigs.

“…It has been shown that a high concen tration of KCI induces sustained contraction of smooth muscle in the absence of external Na+ (7,8). In the present study, we explored the effects of Na+-free, sucrose or Tris …”