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The effects of interleukin-1 beta (IL-1 beta) on the membrane potential and synaptic transmission were examined in neurons of mammalian pelvic ganglia. Bath-application of recombinant human IL-1 beta (6-300 pM) for 10 s-5 min produced a long-lasting hyperpolarization associated with increased input resistance in 11 neurons of rat major pelvic ganglia (MPG). In other 8 neurons, IL-1 beta (300 pM) produced a biphasic response that consists of an initial depolarization followed by a long-lasting hyperpolarization. IL-1 beta 163-171 (10-100 pM), a synthetic nonapeptide analog that contains the active domain of human IL-1 beta, mimicked the effect of IL-1 beta in MPG neurons. gamma-Aminobutyric acid (GABA, 300 microM) produced a depolarization followed by a hyperpolarization that was blocked by picrotoxin (100 microM). Db-cyclic guanosine monophosphate (db-cyclic GMP, 100 microM) also produced an initial depolarization followed by a long-lasting hyperpolarization. These results suggest that the IL-1 beta-induced biphasic response is mediated by a GABA receptor-cyclic GMP pathway. IL-1 beta and IL-1 beta 163-171 caused an initial facilitation followed by a long-lasting depression of the excitatory postsynaptic potential (EPSP) in rabbit VPG. The data suggest that IL-1 beta presynaptically depressed the EPSP by reducing the release of acetylcholine (ACh) from the pelvic nerve terminals.

Effects of Interleukin-1.BETA. on Neurons in Mammalian Pelvic Ganglia.