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

• Published in: Acta physiologica Scandinavica Vol. 165; no. 3; pp. 271 - 276
• Main Authors: WASSDAL, I, NICOLAYSEN, G, IVERSEN, J.-G
• Format: Journal Article
• Language: English
• Published: Oxford UK Blackwell Science Ltd 01-03-1999; Blackwell Science
• Subjects: Acetylcholine - pharmacology; Animals; Apamin - pharmacology; Biological and medical sciences; Bradykinin - pharmacology; calcium; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Calcium-Transporting ATPases - antagonists & inhibitors; Charybdotoxin - pharmacology; Duodenum - drug effects; Duodenum - physiology; Enzyme Inhibitors - pharmacology; Estrenes - pharmacology; Fundamental and applied biological sciences. Psychology; Imidazoles - pharmacology; In Vitro Techniques; Intestine. Mesentery; kinin; Male; Membrane Potentials; Muscle Contraction - drug effects; Muscle Relaxation - drug effects; Muscle, Smooth - drug effects; Muscle, Smooth - physiology; phospholipase C; Potassium Channel Blockers; Pyrrolidinones - pharmacology; Rats; second messenger; Signal Transduction; smooth muscle; Thapsigargin - pharmacology; Type C Phospholipases - antagonists & inhibitors; Vertebrates: digestive system; Duodenum; Rat; Digestive system; Enzyme; Potassium channel antagonist; Rodentia; Contractility; Electrophysiology; Enzyme inhibitor; Esterases; Ionic channel; Phosphoric diester hydrolases; Small intestine; Neuropeptide; Isolated organ; Phospholipase C; Vertebrata; Mammalia; Bradykinin; Second messenger; Hydrolases; Mechanism of action; Potassium
• ISSN: 0001-6772; 1365-201X
• DOI: 10.1046/j.1365-201x.1999.00508.x

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 m
M KCl), 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.