Journal article

Publication year: 2010

Pages: 295-303

Journal: European Journal of Pharmacology

Volume number: 627

Issue number: 1-3

ISSN: 0014-2999

eISSN: 1879-0712

DOI Link: https://doi.org/10.1016/j.ejphar.2009.10.047

Publisher: Elsevier

Abstract: 

Bradykinin acts as an inflammatory mediator in the gut. In the present study we characterized bradykinin-induced changes in the intracellular calcium concentration ([Ca2+](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 [Ca2+]i, in about 90% of the investigated neurones. This Ca2+ 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 fragment 1-8 were ineffective. Immunohistochemical experiments confirmed the presence of bradykinin B-2 receptors in submucosal neurones. The effect of bradykinin on [Ca2+](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 IP3-receptors xestospongin C. Vice versa, the effect of bradykinin was nearly completely dependent on the presence of external Ca2+ and could be reduced by lanthanum, a blocker of voltage-operated Ca2+ channels, suggesting that the bradykinin-induced Ca2+ response is achieved by an influx from the extracellular space via voltage-operated Ca2+ channels.

Harvard Citation style: Avemary, J. and Diener, M. (2010) Effects of bradykinin B2 receptor stimulation at submucosal ganglia from rat distal colon, European Journal of Pharmacology, 627(1-3), pp. 295-303. https://doi.org/10.1016/j.ejphar.2009.10.047

APA Citation style: Avemary, J., & Diener, M. (2010). Effects of bradykinin B2 receptor stimulation at submucosal ganglia from rat distal colon. European Journal of Pharmacology. 627(1-3), 295-303. https://doi.org/10.1016/j.ejphar.2009.10.047