The multiple action of bradykinin on smooth muscle of guinea-pig taenia caeci.
The action of bradykinin on the smooth muscle of guinea-pig taenia caeci was studied by measuring changes in membrane potential, the contractile state of the muscle cells and intracellular calcium concentrations at 22 degrees C in the presence of tetrodotoxin, yohimbine, prazosin, propranolol and atropine. The bradykinin response was characterised by an initial hyperpolarization and suppression of spike activity followed by a sustained depolarization and an increased spike activity accompanied by inhibition of the phasic contractions, an increase in muscle tone and the development of phasic contractions, respectively. The actions of bradykinin were not affected after B1-bradykinin receptors were blocked with des-Arg9-[Leu8]bradykinin. The events induced by bradykinin were accompanied by an increase in the intracellular calcium concentration, as monitored by quin-2 fluorescence. The hyperpolarization and depolarization persisted in the presence of diltiazem (10(-5) M) and in calcium-free conditions. The hyperpolarization could be evoked only once in the absence of calcium and was inhibited in the presence of apamin and after stimulation of alpha 1-adrenoceptors or P2-purinoceptors. Membrane conductance was decreased during the sustained depolarization. The membrane depolarization was abolished after the sodium concentration gradient was reduced. These results show a multiple action of bradykinin mediated via B2-receptors: (1) on calcium mobilization associated with activation of potassium channels; (2) on calcium release from intracellular stores and (3) on receptor-activated sodium channels.
Den Hertog
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A
Department of Pharmacology and Clinical Pharmacology, University of Groningen, The Netherlands.
Nelemans
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A
Van den Akker
J
J
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002432:Cecum / Q000187:drug effects; D002463:Cell Membrane Permeability; D002712:Chlorides / Q000378:metabolism; D004594:Electrophysiology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
D002712:Chlorides; D012964:Sodium; D001920:Bradykinin; D002118:Calcium