IL-1beta and IL-6 excite neurones and suppress cholinergic neurotransmission in the myenteric plexus of the guinea pig.
The effects of the inflammatory mediators interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) on myenteric neurones were investigated by intracellular recordings in a conventional myenteric plexus preparation of guinea pig ileum. Micropressure ejection of IL-1beta and IL-6 (10-7 mol L-1) both caused an excitatory effect in, respectively, 19% (13/70) and 7% (5/70) of the myenteric neurones. The IL-1beta-induced depolarizations were inhibited by superfusion of the IL-1beta receptor antagonist. The responses seen were tetrodotoxin-resistant, indicating a direct neuronal effect. Responses to both cytokines were seen in nitric oxide synthase-immunoreactive as well as choline acetyltransferase-immunoreactive neurones. In addition, both IL-1beta and IL-6 reversibly caused a presynaptic inhibition of acetylcholine release from cholinergic nerve terminals. Both cytokines had no effect on the slow excitatory postsynaptic potentials. Therefore, we can conclude that the inflammatory mediators IL-1beta and IL-6 can act as excitatory neuromodulators of gastrointestinal motility through direct excitatory actions on a subset of myenteric neurones and through the presynaptic inhibition of acetylcholine release.
Kelles
A
A
Center for G.I. Research University of Leuven, Leuven, Belgium.
Janssens
J
J
Tack
J
J
D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives*; D002795:Choline O-Acetyltransferase / Q000032:analysis; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004357:Drug Synergism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005455:Fluorescent Antibody Technique; D005731:Ganglionic Stimulants / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000294:innervation / Q000502:physiology; D066298:In Vitro Techniques; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009197:Myenteric Plexus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D019001:Nitric Oxide Synthase / Q000032:analysis; D012795:Sialoglycoproteins / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D005731:Ganglionic Stimulants; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D012795:Sialoglycoproteins; C070614:neurobiotin; D013779:Tetrodotoxin; D004246:Dimethylphenylpiperazinium Iodide; D001710:Biotin; D019001:Nitric Oxide Synthase; D002795:Choline O-Acetyltransferase