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 b y determining the time course of changes in the cell membrane potentia l, measured with intracellular microelectrodes. A sustained hyperpolar izing effect of BK, which was observed in recently mounted preparation s, became transient after 120 min, when it was followed by depolarizat ion, which was much more evident after 4 h of stretching. As a consequ ence, a parallel increase in the contractile response to BK was also o bserved. The hyperpolarizing effect was due to the opening of Ca2+-dep endent 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 pote ntiating effect of apamin was not observed for acetylcholine. Our resu lts show that the activation of B-2 receptors by BK in the isolated gu inea pig ileum induce a dual effect - hyperpolarization and depolariza tion - 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.