The effect of bradykinin on the electrical activity of rat myenteric neurons

Bradykinin is a mediator involved in inflammatory processes in the gut. Here we investigated the effect of bradykinin on the electrical activity of rat myenteric neurons, the key players for regulation of gastrointestinal motility. Bradykinin (2 × 10(-8)mol/l) induced a biphasic increase in frequency of action potentials measured with microelectrode arrays. This increase was mirrored by a biphasic increase in cytosolic Ca(2+) concentration ([Ca(2+)]i), which was observed in about 40% of the myenteric neurons. The bradykinin B1 receptor agonist des-arg(9)-bradykinin as well as the bradykinin B2 receptor agonist hyp(3)-bradykinin induced a similar effect on [Ca(2+)]i. Immunocytochemical stainings confirmed the expression of both receptor types by myenteric ganglionic cells. Real time PCR showed that the inducible B1 receptor was upregulated during cell culture. The inhibition of cyclooxygenases with piroxicam reduced the effect of bradykinin on the electrical activity of myenteric neurons. The suppression of the glial growth on microelectrode arrays did not affect the bradykinin-induced change in frequency of action potentials. This suggests that prostaglandins, which probably mediate the effect of bradykinin, are not exclusively released from glial cells. The bradykinin-induced increase in [Ca(2+)]i was dependent on the presence of extracellular Ca(2+) and was inhibited by Co(2+), Cd(2+), and Ni(2+), blockers of voltage-dependent Ca(2+) channels, indicating a stimulation of the influx of extracellular Ca(2+) by the kinin. Consequently, bradykinin induces a Ca(2+) influx in myenteric neurons via Ca(2+) channels in the plasma membrane.