Mechanisms of the relaxant and contractile responses to bradykinin in rat duodenum

The signal pathway for bradykinin-induced relaxation followed by contractio n in the isolated rat duodenum was investigated by comparing the effect of blocking agents on the response to bradykinin and acetylcholine. The phosph olipase C inhibitor U-73122 inhibited the relaxation induced by bradykinin, but had no effect on the contraction to either bradykinin or acetylcholine . The same response pattern was observed when the tissues were pre-treated with thapsigargin, a selective inhibitor of microsomal Ca2+ pumps. An inhib itor of non-voltage-dependent Ca2+ influx, SK&F 96365, inhibited the relaxa nt response to bradykinin and the contraction induced by acetylcholine, but not the contraction induced by bradykinin. In Ca2+-free Krebs-Henseleit bu ffer, the tissues failed to respond when they were exposed to either bradyk inin or acetylcholine. When the tissues were partly depolarized (30 mM KCI) , both bradykinin and acetylcholine induced contraction, while the relaxant response to bradykinin was almost completely abolished. Apamin (an antagon ist of low-conductance calcium-activated K+ channel) together with charybdo toxin (CTX, an antagonist of large-conductance calcium-activated K+ channel ) and CTX alone inhibited the relaxant but not the contractile response to bradykinin. We conclude that the biphasic response in isolated rat duodenum to bradykinin involves two distinct pathways. We propose that the relaxant component is induced indirectly via inositol-mediated increase in cytosoli c Ca2+ in non-muscle cells with subsequent signals to the smooth muscle cel ls, whereas the contractile response is induced by direct effect on the smo oth muscle cells.