Depressant effects of hypoxia and hypoglycaemia on neuro‐effector transmission of guinea‐pig intestine studied in vitro with a pharmacological model

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Abstract
Since intermittent ischaemia may play an important role in the ætiology of Inflammatory Bowel Disease, particularly Crohn's Disease, a pharmacological model of neuronal ischaemia was applied to guinea‐pig isolated intestinal preparations to mimic the acute effects of reduced blood flow on intestinal motility. Neuro‐effector transmission and smooth muscle performance were examined in myenteric plexus‐longitudinal muscle preparations of guinea‐pig ileum exposed to sodium cyanide (NaCN), in order to inhibit oxidative phosphorylation, or to iodoacetic acid (IAA), to block glycolysis. Comparisons were made with the effects due to simple deprivation of oxygen or glucose. Depressions of cholinergic neuro‐effector transmission induced by hypoxia or NaCN (effective concentration range 0.1–3 mm), given as separate treatments, singly or repetitively over 60–90 min, were apparent within 30 s and were reversible. The maximum inhibition was 90% and the IC50 for NaCN was 0.3 mm. A conspicuous component of these inhibitions was prejunctional. Non‐cholinergic neuro‐effector contractions were inhibited by up to 90% by anoxia or NaCN but recovery was incomplete and slower than with cholinergic contractions. Glucose‐free solutions also caused a reversible failure of cholinergic neuro‐effector transmission but of slower onset. In contrast, IAA (0.06–1 mm) abolished contractions irreversibly, apparently by a direct depressant effect on smooth muscle contraction. Unlike NaCN, IAA caused an initial potentiation of electrically‐induced contractions, partly by a prejunctional potentiation of cholinergic neuro‐effector transmission. It is concluded that a disruption of intestinal activity in pathological conditions associated with intestinal ischaemia may result from disturbances in the function of enteric neurones. British Journal of Pharmacology (1997) 120, 107–115; doi:10.1038/sj.bjp.0700870