Enhancement by prostaglandin E2 of bradykinin activation of embryonic rat sensory neurones.
1. The capacity of prostaglandin E2 (PGE2) to enhance the excitatory response elicited by bradykinin in embryonic rat sensory neurones grown in culture was investigated using the whole-cell patch-clamp recording technique. 2. The focal application of bradykinin (BK) produced a small concentration-dependent depolarization that was associated with an inward current and was described by a ligand-binding isotherm having an EC50 of 230 nM. Typically the depolarization was accompanied by action potentials (APs). 3. After pretreatment with 1 microM PGE2 for 10 min, the number of APs elicited by 100 nM BK was increased by about 3-fold. However, PGE2 had no effect on the amplitude of either the BK-elicited depolarization or inward current. The addition of 1 or 10 microM PGE2 had no effect on the resting membrane potential. 4. In all neurones exhibiting PGE2-enhanced excitability, there was a decrease in the amount of injected current necessary to elicit an AP. 5. The enhanced excitability was not due to repeated exposure to BK since neither the amplitude of the BK-evoked depolarization nor the number of APs was altered by the application of BK at 2 min intervals over a period of 30 min. 6. These results are consistent with the notion that PGE2 acts directly on sensory neurones to enhance the response to chemical excitatory agents, like BK, by lowering the AP firing threshold. The PGE2-mediated sensitization does not result from an alteration of the resting potential or modulation of the neuronal response to the chemical agonist.
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Department of Pharmacology and Toxicology, School of Medicine, Indiana University, Indianapolis 46202-5120.
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D004056:Differential Threshold / Q000187:drug effects; D015232:Dinoprostone / Q000494:pharmacology*; D004357:Drug Synergism; D004594:Electrophysiology; D008564:Membrane Potentials / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects* / Q000502:physiology; D051381:Rats
D015232:Dinoprostone; D001920:Bradykinin