Prevention of the excitatory actions of bradykinin by inhibition of PGI2 formation in nodose neurones of the guinea-pig.
1. Intracellular recordings were made from neurones in intact guinea-pig nodose ganglia in vitro and from acutely isolated adult guinea-pig and rabbit nodose neurons to study a bradykinin (BK)-mediated block of a slow spike after-hyperpolarization (AHPslow) that is prominent in 30-40% of these neurones. 2. BK (100 nM) reversibly blocked the AHPslow, resulting in an ablation of the spike accommodative properties of these neurones. The B1 BK receptor agonist [des-Arg9]-BK did not mimic or prevent the actions of BK. In contrast, the B2 BK receptor antagonist D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]-BK (HOE 140) prevented BK-induced block of the AHPslow and the effect of BK on spike frequency adaptation. 3. The BK block of the AHPslow in acutely dissociated neurones was prevented by indomethacin, indicating that this BK effect was dependent upon a cyclo-oxygenase metabolite intrinsic to these neurones. 4. One to twenty femtomoles of the prostanoids PGE2, PGD2, 9 alpha, 11 beta-PGF2 (a metabolite of PGD2), PGF2 alpha, TxB2 and PGI2 were released spontaneously from a nodose ganglion in 15 min. BK (100 nM) selectively increased PGI2 release 2.8-fold without affecting the release of the other prostanoids. Treatment with 10 microM tranylcypromine (TCP), a putative PGI2 synthase inhibitor, completely prevented the BK-induced release of PGI2. 5. In the presence of 10 microM TCP, BK no longer produced significant effects on the AHPslow. In contrast, 10 microM TCP did not prevent PGI2 from blocking the AHPslow. 6. These results suggest that vagal afferents that exhibit AHPslow also possess the B2 type of BK receptor. Activation of these BK receptors results in the production of PGI2, which in turn controls spike frequency adaptation by affecting the amplitude of the AHPslow.
Weinreich
D
D
University of Maryland School of Medicine, Department of Pharmacology and Experimental Therapeutics, Baltimore 21201-1559, USA.
Koschorke
G M
GM
Undem
B J
BJ
Taylor
G E
GE
D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D004594:Electrophysiology; D011464:Epoprostenol / Q000037:antagonists & inhibitors*; D006168:Guinea Pigs; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000378:metabolism*; D009620:Nodose Ganglion / Q000166:cytology / Q000378:metabolism*; D011817:Rabbits; D018002:Receptors, Bradykinin / Q000187:drug effects / Q000502:physiology; D014191:Tranylcypromine / Q000494:pharmacology
D018002:Receptors, Bradykinin; D014191:Tranylcypromine; C065679:icatibant; D011464:Epoprostenol; D001920:Bradykinin; D007213:Indomethacin