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

1. This study was performed to elucidate the role of prostaglandins in the action of bradykinin on serosal afferent neurones sup-plying the rat jejunum. Extracellular recordings of multiunit 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 mu M and is consistent with an interaction at the B-2 receptor subtype. 3. The stimulatory effect of bradykinin on serosal afferents was antagonized by a specific antagonist of the B-2 receptor, HOE140. In contrast, a selective B-1 receptor antagonist, [des-Arg(10)]HOE140, had no effect. The IC50 estimate obtained for HOE140 was 1.6 nM and again consistent with an interaction at B-2 receptors. 4. The response to a submaximal concentration of bradykinin (1 mu M) was significantly reduced to 24.4 +/- 54.9% of control following blockade of cyclo-oxygenase activity with naproxen (10 mu M). The addition of 1 mu M prostaglandin E-2 (PGE(2)), in the presence of naproxen, had no direct effect on afferent activity, but fully restored the response to bradykinin in 15 single a,afferents. 5. In summary bradykinin stimulates serosal afferents by a direct action on kinin B-2 receptors that are present on serosal afferent terminals. The response to bradykinin is dependent on the presence of prostaglandins, particularly PGE(2). We suggest that bradykinin has a self-sensitizing action, whereby it stimulates the release of PGE(2), which in turn sensitizes the endings of serosal afferent neurones responsive to bradykinin.