New evidence on the mechanisms underlying bradykinin-mediated contraction of the pig iris sphincter in vitro

Abstract

We have reported previously that bradykinin (BK) induces potent and reproducible concentration-dependent contractions of the pig iris sphincter (PIS) muscle in vitro through the activation of BK B 2 receptors. Here we attempted to investigate additional mechanisms by which BK induces contraction of the PIS in vitro. BK-mediated contraction of the PIS relied largely on the external Ca 2+ influx by a mechanism sensitive to the L-, N- and P-type of Ca 2+ channel selective blockers. Likewise, BK-induced contraction of the PIS was greatly inhibited by the CGRP-(8–37), NK 2 or NK 3 receptor antagonists (SR 48968, SR 142801), and to a lesser extent by the NK 1 antagonist (FK 888). Capsaicin desensitization of PIS or capsazepine pre-incubation also significantly reduced BK-mediated contraction in the PIS. Furthermore, KT 5720 or GF 109203X (the protein kinase A and C inhibitors, respectively) also significantly inhibited BK-mediated contraction. Taken together, these results indicate that BK-mediated contraction of the PIS seems to be mediated primarily by the release of CGRP and tachykinins from sensory nerve fibers, and relies largely on extracellular Ca 2+ influx via activation of L-, N- and P-type of Ca 2+ channels. Finally, these responses are mediated by activation of both protein kinase A- and C-dependent mechanisms.