Mechanism of smooth muscle contraction and relaxation mediated by kinin receptor

The increase in sensitivity of guinea pig preparations to bradykinin (BK) due to stretching occurring with time after mounting was studied by determining the time course of changes in the cell membrane potential, measured with intracellular microelectrodes. A sustained hyperpolarizing effect of BK, which was observed in recently mounted preparations, became transient after 120 min, when it was followed by depolarization, which was much more evident after 4 h of stretching. As a consequence, a parallel increase in the contractile response to BK was also observed. The hyperpolarizing effect was due to the opening of Ca(2+)-dependent K+ channels sensitive to apamin, since BK dose-response curves done within 1 h of mounting were shifted to the left, becoming similar to dose-response curves obtained 4 h after mounting of the guinea pig ileum preparation. These results were specific for BK, since the potentiating effect of apamin was not observed for acetylcholine. Our results show that the activation of B2 receptors by BK in the isolated guinea pig ileum induce a dual effect--hyperpolarization and depolarization--and that the increase in the contractile response consequent to stretching is probably due to the inactivation of apamin-sensitive Ca(2+)-dependent K+ channels.