A DISTINCTIVE ELECTROPHYSIOLOGICAL SIGNATURE FROM THE PEYERS-PATCHES OF RABBIT INTESTINE

1 Rabbit small intestinal segments containing Peyer's patches (PP) wer e examined in Ussing chambers using short-circuit current (I-sc) recor ding. By comparison with control small intestinal mucosal segments, ra bbit PP-containing epithelia exhibited decreased basal I-sc, increased transepithelial resistance (TER) and unchanged potential difference ( PD). 2 Carbachol caused a decrease in I-sc in rabbit PP epithelia. For skolin, dibutyryl cyclic GMP, histamine and the calcium ionophore, A23 187, were without effect. In contrast, control epithelial segments of rabbit intestine responded to carbachol and forskolin with an increase d I-sc, indicative of electrogenic chloride secretion. The EC(50) for carbachol was approximately 2 mu M in both types of epithelia. Methach oline also caused an outward current in rabbit PP epithelia which had similar properties to that of carbachol. The effect of the cholinomime tics on rabbit PP was basolateral-sided, reversible, and sensitive to low concentrations of the general muscarinic cholinoceptor blockers, a tropine, scopolamine and also to the M(1) cholinoceptor blocker, piren zepine. 3 The I-sc response to cholinomimetics in rabbit PP was insens itive to bumetanide, amiloride, TEA, barium, acetazolamide, piroxicam and omeprazole, but was attenuated in the presence of ouabain. Using b ilaterally-substituted solutions, the carbachol effect on rabbit PP I- sc was abolished in chloride/bicarbonate-free, but not in chloride-fre e solutions, suggestive of stimulation of electrogenic bicarbonate abs orption by the agent. Substitution for sodium abolished both the basal current and the I-sc response to carbachol. Part of the effect of car bachol on PP I-sc appeared to be mediated by submucosal neurones becau se addition of tetrodotoxin reduced the effect by 60%. 4 As microfold (M) epithelial cells predominate in the PP of the rabbit, the unusual phenotype of cholinomimetic-induced outward current may be used as an electrophysiological marker for these potential sites of oral vaccine delivery, and in particular it may also be of use as a marker for rabb it M cells.