Electrical behaviour of interleukin‐1 beta (IL‐1β) and prostaglandin‐E2 (PGE₂) on colonic myenteric neurones

Abstract

Intracellular recordings were used to examine the effects on electrical and synaptic behaviour of interleukin (IL)-1beta and prostaglandin E2(PGE2) on myenteric neurones of the guinea-pig colon. Application of IL-1beta and PGE2resulted in a concentration-dependent slow depolarization with enhanced spike discharge in, respectively, 45% (21/47) and 83% (33/41) of the impaled colonic neurones. Administration of IL-1beta in three neurones (6%) elicited a hyperpolarization. Responses remained during tetrodotoxin application, indicative of a direct effect of both substances on the impaled neurones. The effects of IL-1beta remained in the presence of indomethacine, a prostaglandin synthase inhibitor. Responses were seen in both nitric oxide synthase- and choline acetyl transferase-immunoreactive neurones. IL-1beta evoked a 26% reduction of the fast excitatory postsynaptic potential. These results indicate that the application of IL-1beta and PGE2evoke direct excitatory actions on a subset of myenteric neurones. For IL-1beta, direct inhibition and presynaptic inhibition of the fast excitatory postsynaptic potential has also been found. In the distal colon, responses to IL-1beta are not mediated through PGE2pathways.

Prolonged IL-1β exposure alters neurotransmitter and electrically induced Ca2+responses in the myenteric plexus

“…The excitatory effect of acute superfusion of IL‐1β of this study is in agreement with previous findings of electrophysiological experiments with IL‐1 on myenteric and submucosal neurones in the ileum and in the colon of guinea pigs 8,9,25 . In these reports, slightly more neurones were cholinergic in nature than in our study.…”

“…We speculate that the concentration‐specific effects may result from excitation at lower cytokine concentrations that is be counterbalanced by inhibitory mechanisms occurring at higher concentrations. Previous electrophysiological studies pointed towards a dual action of IL‐1β, not only including postsynaptic excitation, but also presynaptic inhibition of neurotransmitter release 9 . It is conceivable that postsynaptic excitation is predominant at lower concentrations, whereas presynaptic inhibition is only effective at higher concentrations.…”

“…More recently, discrete immunological changes such as an enhanced expression of IL‐1β by unstimulated peripheral blood mononuclear cells were shown to be present in IBS patients 7 . Earlier electrophysiological studies already demonstrated an excitatory effect of IL‐1β on ileal and colonic myenteric neurones in the guinea pig 8,9 . Subsequent studies analyzing Fos expression indicated that IL‐1β mostly activated NOS‐ and enkephalin‐expressing neurones 10 .…”

Changes in colonic motility and the electrophysiological properties of myenteric neurons persist following recovery from trinitrobenzene sulfonic acid colitis in the guinea pig

“…However, in the current study colonic motility was not restored by postinflammatory administration of the COX‐2 inhibitor, DFU. Furthermore, the AH neurons, which are sensitive to PGE 2 , 36,37 were still hyperexcitable even though PGE 2 levels are not elevated at this time point but is at the 6‐day time point 18 . Collectively, these data suggest that the changes occur during the active state of inflammation potentially through a COX‐2 sensitive mechanism, but once initiated do not require sustained elevations in COX‐2 derived prostaglandins to maintain them.…”

Alterations of the myenteric plexus of the ileum and the descending colon caused by Toxoplasma gondii (genotype III)

“…Mast cells produce bradykinin which eases the enteric secretion of acetylcholine 26 , besides increasing the excitability of the myenteric neurons 27 and primary intestinal afferents 28 . The muscle macrophages secrete cytokines such as IL-1β and IL-6, which act directly on the increase of the excitability of the myenteric neurons 29 and module the secretion of norepinephrine 30 . Moreover, the intestinal inflammation induces the secretion of cytokines such as IL-1β, TNF-α, IFN-g, and TGF-β from the myenteric neurons; however, the identity of the cells which secrete cytokines, neuronal and glias, is not known 25 .…”