Cholinergic-mediated secretion in the rat colon: neuronal and epithelial muscarinic responses

The acetylcholine receptor agonists, acetylcholine (10(-5)-10(-4 M), carbachol (5 x 10(-6)-5 x 10(-5) M), bethanechol (5 x 10(-5)-5 x 10(-4) M) and dimethylphenylpiperazinium (DMPP, 10(-5) M) increased the short-circuit current (Isc) in the rat colon descendens by a tetrodotoxin (TTX)-sensitive mechanism. Blockade by TTX was still observed after removal of the submucosa, indicating the involvement of neurons of the mucosal plexus. Hexamethonium (10(-5) M) and atropine (10(-6) M) were used to distinguish between nicotinic and muscarinic neuronally mediated effects. The inhibitor of choline uptake, hemicholinium-3 (1 mM), reversibly inhibited the effect of repeated electric field stimulation (EFS). The EFS response was only inhibited by high concentrations of atropine (greater than or equal to 10(-5) M). In mucosa-submucosa preparations 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) was more effective than telenzepine whereas pirenzepine was ineffective. Pirenzepine inhibited the EFS response in mucosa preparations as did telenzepine and 4-DAMP. It was not possible to differentiate between the muscarinic receptors involved in the different parts of the enteric nervous system on the basis of our results.