Role of bradykinin B 2 receptors in the modulation of the peristaltic reflex of the guinea pig isolated ileum

Abstract

Bradykinin is well known to have a biphasic action to contract and relax gastrointestinal tissue. However, no studies have investigated the potential action of bradykinin to affect the peristaltic reflex. In the present study, serosally applied bradykinin (1–1000 nM) and the bradykinin B 2 receptor agonist, kallidin (1–1000 nM), had inhibitory actions and increased the pressure threshold for peristalsis (maximum changes seen at 1000 nM were ∼60 Pa), as did morphine (IC 50 = 22.3 ± 4.8 nM; maximum increase in the pressure threshold was ∼130 Pa). Conversely, the B 1 kinin receptor agonist, [des-Arg 9]-bradykinin (1–1000 nM), had no effect ( P > 0.05). Two potent B 2 receptor antagonists, FR173657 (1 and 100 nM) and icatibant (10 nM), significantly antagonized the inhibitory action of serosally applied bradykinin on peristalsis ( P < 0.01), whilst the B 1 receptor antagonist, Lys-[des-Arg 9, Leu 8]-bradykinin (100 nM) was inactive ( P > 0.05). In comparison, 5-hydroxytryptamine (1–1000 nM) facilitated peristalsis (EC 50 = 37.7 ± 23.0 nM; maximum reduction of the pressure threshold for peristalsis was ∼76 Pa), as did FR173657 at 100 nM (reducing the pressure threshold for peristalsis by ∼15 Pa; P < 0.05) but icatibant at 10 nM was inactive ( P > 0.05). The results indicate that bradykinin B 2 receptors mediate an inhibition of peristalsis in the guinea pig isolated ileum.