Role of bradykinin B2 receptors in the modulation of the peristaltic reflex of the guinea pig isolated ileum.
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 B2 receptor agonist, kallidin (1-1000 nM), had inhibitory actions and increased the pressure threshold for peristalsis (maximum changes seen at 1000 nM were approximately 60 Pa), as did morphine (IC50=22.3+/-4.8 nM; maximum increase in the pressure threshold was approximately 130 Pa). Conversely, the B1 kinin receptor agonist, [des-Arg9]-bradykinin (1-1000 nM), had no effect (P>0.05). Two potent B2 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 B1 receptor antagonist, Lys-[des-Arg9, Leu8]-bradykinin (100 nM) was inactive (P>0.05). In comparison, 5-hydroxytryptamine (1-1000 nM) facilitated peristalsis (EC50=37.7+/-23.0 nM; maximum reduction of the pressure threshold for peristalsis was approximately 76 Pa), as did FR173657 at 100 nM (reducing the pressure threshold for peristalsis by approximately 15 Pa; P<0.05) but icatibant at 10 nM was inactive (P>0.05). The results indicate that bradykinin B2 receptors mediate an inhibition of peristalsis in the guinea pig isolated ileum.
Chan
Siu Ki
SK
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.
Rudd
John A
JA
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D065094:Bradykinin B2 Receptor Antagonists; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007609:Kallidin / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010528:Peristalsis / Q000187:drug effects*; D011312:Pressure; D011804:Quinolines / Q000494:pharmacology; D043782:Receptor, Bradykinin B2 / Q000819:agonists / Q000502:physiology*; D012018:Reflex / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology
D065094:Bradykinin B2 Receptor Antagonists; C105311:FR 173657; D011804:Quinolines; D043782:Receptor, Bradykinin B2; C082229:bradykinin, Lys-Leu(8)-desArg(9)-; C024626:bradykinin, des-Arg(9)-; D012701:Serotonin; D007609:Kallidin; D009020:Morphine; C065679:icatibant; D001920:Bradykinin