Cholinergic receptors mediating secretion in guinea pig colon.

This study examined the role of cholinergic receptors in mediating the chloride secretory response evoked by stimulation of enteric neurons in muscle-stripped segments of mucosa from guinea pig distal colon set up in flux chambers. Basal short-circuit current was not altered by tetrodotoxin, hexamethonium or muscarinic antagonists. The neurally evoked response was not altered by hexamethonium, but was reduced by muscarinic antagonists with a rank order of potency: atropine = 4-diphenyl acetoxy-N-methylpiperidine greater than pirenzepine. 1,1-Dimethyl-4-phenyl-piperazinium iodide increased resting short-circuit current above basal levels. Carbachol and bethanechol evoked a concentration-dependent increase in short-circuit current that was reduced by tetrodotoxin. The effects of carbachol were antagonized by hexamethonium, 4-diphenyl acetoxy-N-methylpiperidine and pirenzepine. Competition for [3H]quinuclidinyl benzilate binding indicated a rank order of potency of 4-diphenyl acetoxy-N-methylpiperidine greater than pirenzepine greater than carbachol greater than bethanechol. These studies indicate that cholinergic and noncholinergic transmission play a significant role in regulation of chloride transport in the guinea pig distal colon. Both nicotinic and muscarinic receptors on neurons that project to the mucosa as well as epithelial muscarinic receptors are mediators of the chloride secretory response.