D. Weinreich et al., PREVENTION OF THE EXCITATORY ACTIONS OF BRADYKININ BY INHIBITION OF PGI(2) FORMATION IN NODOSE NEURONS OF THE GUINEA-PIG, Journal of physiology, 483(3), 1995, pp. 735-746
1. Intracellular recordings were made from neurones in intact guinea-p
ig nodose ganglia in vitro and from acutely isolated adult guinea-pig
and rabbit nodose neurones to study a bradykinin (BK)-mediated block o
f a slow spike after-hyperpolarization (AHP(slow)) that is prominent i
n 30-40% of these neurones. 2. BK (100 nm) reversibly blocked the AHP(
slow), resulting in an ablation of the spike accommodative properties
of these neurones. The B1BK receptor agonist [des-Arg(9)]-BK. did not
mimic or prevent the actions of BK. In contrast, the B2BK receptor ant
agonist D-Arg-[Hyp(3), Thi(5), D-Tic(7), Oic(8)] BK (HOE 140) prevente
d BK-induced block of the AHP(slow) and the effect of BK on spike freq
uency adaptation. 3. The BK block of the AHP(slow) in acutely dissocia
ted neurones was prevented by indomethacin, indicating that this BK ef
fect was dependent upon a cyclo-oxygenase metabolite intrinsic to thes
e neurones. 4. One to twenty femtomoles of the prostanoids PGE(2), PGD
(2), 9 alpha, 11 beta-PGF(2) (a metabolite of PGD(2)), PGF(2 alpha), T
xB(2) and PGI(2) were released spontaneously from a nodose ganglion in
15 min. BK (100 nm) selectively increased PGI(2) release 2.8-fold wit
hout affecting the release of the other prostanoids. Treatment with 10
mu M tranylcypromine (TCP), a putative PGI(2) synthase inhibitor, com
pletely prevented the BK-induced release of PGI(2). 5. In the presence
of 10 mu M TCP, BK. no longer produced significant effects on the AHP
slow. In contrast, 10 mu M TCP did not prevent PGI(2) from blocking th
e AHP(slow). 6. These results suggest that vagal afferents that exhibi
t AHP(slow) also possess the B-2 type of BK receptor. Activation of th
ese BK receptors results in the production of PGI(2), which in turn co
ntrols spike frequency adaptation by affecting the amplitude of the AH
P(slow).