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

Abstract

The signal pathway for bradykinin-induced relaxation followed by contraction in the isolated rat duodenum was investigated by comparing the effect of blocking agents on the response to bradykinin and acetylcholine. The phospholipase 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 inhibitor of non-voltage-dependent Ca2+ influx, SK&F 96365, inhibited the relaxant response to bradykinin and the contraction induced by acetylcholine, but not the contraction induced by bradykinin. In Ca2+-free Krebs-Henseleit buffer, the tissues failed to respond when they were exposed to either bradykinin 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 antagonist of low-conductance calcium-activated K+ channel) together with charybdotoxin (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 cytosolic Ca2+ in non-muscle cells with subsequent signals to the smooth muscle cells, whereas the contractile response is induced by direct effect on the smooth muscle cells.

Receptors and mechanisms mediating the biphasic response evoked by bradykinin in rat colonic smooth muscle

“…[2][3][4][5]8 Similar findings have been made in guinea pig ileum 22 and colon. 6 The results of the isometric contraction measurements in this study as well as the original observations by Elliot et al 13 show that rat colon responds in a similar manner as described for duodenum.…”

“…It has been shown that rat duodenum responds to bradykinin in a biphasic manner, i.e., a relaxation followed by a contraction, 4,5,9,10,12 whereas the knowledge about changes in colonic motility induced by this mediators is scarce. 13 Thus, changes in isometric force in the rat colon induced by bradykinin were investigated.…”

“…In initial studies on rat duodenum, where bradykinin induces a relaxation followed by a contraction, it was hypothesized that B 2 receptors mediate the relaxation and B 1 receptors the contraction. 2,3 Later studies on the same tissue together with studies performed on smooth muscle preparations from guinea pig suggested the involvement of apamin-sensitive Ca 2+ -activated K + channels in the relaxation induced by the kinin, [4][5][6][7][8][9] which would hyperpolarize the membrane after the IP 3 -mediated Ca 2+ release from the endoplasmic reticulum. 5 It was also proposed by these authors that a part of the response evoked by the kinin might be mediated by adherent non-muscle cells.…”

The bradykinin BK2 receptor mediates angiotensin II receptor type 2 stimulated rat duodenal mucosal alkaline secretion

“…Bradykinin and kallikrein are both inactivated by kininase II (angiotensin converting enzyme). Pharmacological actions of bradykinin in the gastrointestinal tract include vasodilation (due to release of NO and PGI2), increased vascular permeability, and stimulation of epithelial ion and fluid transport [21,22] Bradykinin has been shown to be involved in longitudinal duodenal motor activity [23] and to elicit relaxant response in cultured duodenal smooth muscle cells [24]. Bradykinin induces duodenal mucosal alkaline secretion and the receptor has been proposed to be the BK2 receptor, since such secretory stimulation was blocked by intravenous administration of HOE140 [8].…”

Bradykinin modulates pacemaker currents through bradykinin B2 receptors in cultured interstitial cells of Cajal from the murine small intestine

“…IP 3 mobilizes Ca 2+ from endoplasmic reticulum and diacylglycerol activates protein kinase C (Ellis & Fozard, 2002). Bradykinin contracts colon circular muscles or ileal longitudinal muscles by IP 3 generation and elevates cytosolic Ca 2+ concentration in rat duodenal smooth muscle cells by the release of Ca 2+ from internal storage (Ransom et al ., 1992; Hasler et al ., 1995; Wassdal et al ., 1999). In addition, the generation of pacemaker currents was dependent on intracellular Ca 2+ oscillation.…”