ENHANCEMENT BY PROSTAGLANDIN E(2) OF BRADYKININ ACTIVATION OF EMBRYONIC RAT SENSORY NEURONS

1. The capacity of prostaglandin E(2) (PGE(2)) to enhance the excitato ry response elicited by bradykinin in embryonic rat sensory neurones g rown in culture was investigated using the whole-cell patch-clamp reco rding technique. 2. The focal application of bradykinin (BK) produced a small concentration-dependent depolarization that was associated wit h an inward current and was described by a ligand-binding isotherm hav ing an EC(50) of 230 nM. Typically the depolarization was accompanied by action potentials (APs). 3. After pretreatment with 1 mu M PGE(2) f or 10 min, the number of APs elicited by 100 nM BK was increased by ab out 3-fold. However, PGE(2) had no effect on the amplitude of either t he BK-elicited depolarization or inward current. The addition of 1 or 10 mu M PGE(2) had no effect on the resting membrane potential. 4. In all neurones exhibiting PGE(2)-enhanced excitability, there was a decr ease in the amount of injected current necessary to elicit an AP. 5. T he enhanced excitability was not due to repeated exposure to BK since neither the amplitude of the BK-evoked depolarization nor the number o f APs was altered by the application of BK at 2 min intervals over a p eriod of 30 min. 6. These results are consistent with the notion that PGE(2) acts directly on sensory neurones to enhance the response to ch emical excitatory agents, like BK, by lowering the AP firing threshold . The PGE(2)-mediated sensitization does not result from an alteration of the resting potential or modulation of the neuronal response to th e chemical agonist.