The role of prostaglandins in the bradykinin‐induced activation of serosal afferents of the rat jejunum in vitro

Abstract

1 This study was performed to elucidate the role of prostaglandins in the action of bradykinin on serosal afferent neurones supplying the rat jejunum. Extracellular recordings of multi‐unit activity were made from serosal afferents in isolation, using a novel in vitro preparation. The discharge of single afferents within the multi‐unit recording was monitored using waveform discrimination software. 2 All afferents tested were both mechano‐ and capsaicin sensitive. Application of bradykinin elicited increases in whole nerve discharge in a concentration‐dependent manner. The agonist potency estimate (EC₅₀) was 0.62 ± 0.12 μm and is consistent with an interaction at the B₂ receptor subtype. 3 The stimulatory effect of bradykinin on serosal afferents was antagonized by a specific antagonist of the B₂ receptor, HOE140. In contrast, a selective B₁ receptor antagonist, [des‐Arg¹⁰]HOE140, had no effect. The IC₅₀ estimate obtained for HOE140 was 1.6 nm and again consistent with an interaction at B₂ receptors. 4 The response to a submaximal concentration of bradykinin (1 μm) was significantly reduced to 24.4 ± 54.9% of control following blockade of cyclo‐oxygenase activity with naproxen (10 μm). The addition of 1 μm prostaglandin E₂ (PGE₂), in the presence of naproxen, had no direct effect on afferent activity, but fully restored the response to bradykinin in 15 single afferents. 5 In summary, bradykinin stimulates serosal afferents by a direct action on kinin B₂ receptors that are present on serosal afferent terminals. The response to bradykinin is dependent on the presence of prostaglandins, particularly PGE₂. We suggest that bradykinin has a self‐sensitizing action, whereby it stimulates the release of PGE₂, which in turn sensitizes the endings of serosal afferent neurones responsive to bradykinin.