Cholinergic inhibition of electrogenic sodium absorption in the guinea pig distal colon

Submucosal cholinergic and noncholinergic neurons in intestines have been shown to be involved in regulating epithelial transport functions, particularly stimulating [Cl.sup.-] secretion. This study investigates the role of submucosal cholinergic neurons in regulating electrogenic [Na.sup.+] absorption in distal colon. Amiloride-sensitive short-circuit current ([I.sub.sc]) and [sup.22][Na.sup.+] flux were measured in mucosal and mucosal-submucosal preparations mounted in Ussing chambers. In the mucosal preparation, carbachol (CCh) added to the serosal side inhibited amiloride-sensitive [I.sub.sc] and amiloride-sensitive [sup.22][Na.sup.+] absorption. The inhibitory effect of CCh was observed at ~0.1 [micro]M, and maximum inhibition of ~70% was attained at ~30 [micro]M (I[C.sub.50] = ~1 [micro]M). CCh-induced inhibition of amiloride-sensitive [I.sub.sc] was almost totally abolished by 10 [micro]M atropine. Treatment of the tissue with ionomycin markedly reduced amiloride-sensitive [I.sub.sc], but a subsequent addition of CCh further decreased it. Also, CCh still had an inhibitory effect, although significantly attenuated, after the tissue had been incubated with a low-[Ca.sup.2+] solution containing ionomycin and BAPTA-AM. Applying electrical field stimulation to submucosal neurons in the mucosal-submucosal preparation resulted in inhibition of amiloride-sensitive [I.sub.sc], ~33% of this inhibition being atropine sensitive. Physostigmine inhibited amiloride-sensitive [I.sub.sc], this effect being abolished by atropine. In conclusion, submucosal cholinergic and noncholinergic neurons were involved in inhibiting electrogenic [Na.sup.+] absorption in colon. This inhibition by cholinergic neurons was mediated by muscarinic receptor activation. enteric nerve; intracellular [Ca.sup.2+]; acetylcholine; intestinal secretion; epithelial [Na.sup.+] channel