| Title | Effects of bradykinin B(2) receptor stimulation at submucosal ganglia from rat distal colon. | | Author(s) | Avemary J, Diener M | | Institution | Institute for Veterinary Physiology, University of Giessen, Germany. | | Source | Eur J Pharmacol 2009 Oct 27. | | Abstract | Bradykinin acts as inflammatory mediator in the gut. In the present study we characterized bradykinin-induced changes in the intracellular calcium concentration ([Ca(2+)](i)) in whole mount submucosal preparations from rat distal colon and examined the bradykinin receptors and subsequent signalling cascades involved. Bradykinin (2.10(-10) - 2.10(-7)mol/l) evoked a concentration-dependent increase in [Ca(2+)](i) in about 90% of the investigated neurones. This Ca(2+) response was abolished by the bradykinin B(2) receptor antagonist HOE 140. The B(2) receptor agonist [Hyp(3)]-bradykinin mimicked the kinin response. In contrast, the B(1) receptor antagonist [des-Arg(10)]-HOE 140 and the B(1) receptor agonist bradykinin fragment1-8 were ineffective. Immunohistochemical experiments confirmed the presence of bradykinin B(2) receptors in submucosal neurones. The effect of bradykinin on [Ca(2+)](i) was not mediated by a release of prostaglandins, as it was resistant against the cyclooxygenase inhibitor indomethacin. Blocking of G(q/11) proteins with YM-254890 suppressed the action of bradykinin, revealing that neuronal bradykinin B(2) receptors are coupled to this G protein. However, the subsequent signalling cascade differed from the classical phospholipase C signalling pathway, as the bradykinin response was resistant against the phospholipase C inhibitor U-73221, the ryanodine receptor antagonist dehydroryanodine, and only marginally sensitive against the blocker of IP(3)-receptors xestospongin C. Vice versa, the effect of bradykinin was nearly completely dependent on the presence of external Ca(2+) and could be reduced by lanthanum, a blocker of voltage-operated Ca(2+) channels, suggesting that the bradykinin-induced Ca(2+) response is achieved by an influx from the extracellular space via voltage-operated Ca(2+) channels. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19878667 |
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