Changes in the Pannexin Channel in Ileum Myenteric Plexus and Intestinal Motility Following Ischemia and Reperfusion

Background: Intestinal ischemia affects the functioning of the Enteric Nervous System (ENS). Pannexin-1 channel participates in cell communication and extracellular signaling. Probenecid (PB) is a pannexin-1 channel inhibitor, which can be a potential treatment for intestinal ischemia.

Aim: Study the effects of ileal ischemia and reperfusion (I/R) and PB treatment on myenteric neurons and in rats.

Methods: Male Wistar rats were used for I/R induction, the ileal vessels were occluded for 45 min and reperfusion was performed after this time. The Sham groups underwent all surgical procedures without obstruction of the ileal vessels. Animals were euthanized 24 h or 14d post-I/R. The PB group received an injection of PB post-I/R. Ileal segments were collected for immunofluorescence analyses to identify neurons calretinin immunoreactive (-ir) and pannexin-1-ir. Neuronal density (cells/field), area (μm²), intestinal motility, and ultrastructural analyses were performed.

Key results: The pannexin-1 channel was double-labeled with calretinin-ir neurons. Neuronal density reduced by 21% reduction in calretinin-ir neurons in the I/R 24 h group and recovered 26% in the PB 24 h group. In the 14d group, there was a 23% reduction in calretinin-ir neurons in the I/R 14d group and a recovery of 26% in the PB 14d group. The analysis of the contraction after electrical simulation was lower in the I/R 14 d group and recovered in the PB 14d.

Conclusions and inferences: Intestinal I/R affects myenteric neurons and causes morphological and functional changes. PB was able to attenuate the effects of I/R and could constitute a therapeutic tool for intestinal I/R.