The effect of drugs acting on cholinoceptors and mucosal chloride on luminal bicarbonate transport by rat caecum under in vitro conditions

Abstract

1. The transport of HCO3- (Jsm) from a HCO3(-)-buffered serosal to an unbuffered mucosal saline solution has been studied in rat caecum in vitro. 2. Carbachol, bethanechol and acetylcholine (ACh) caused a concentration-dependent fall in Jsm with similar maximum effects. 1,1-Dimethyl-4-phenyl-piperazinium iodide (DMPP) also inhibited Jsm but the effect was less than with the other drugs. Maximum cholinoceptor inhibition was less than that obtained with anoxia. 3. Responses were blocked by atropine (10(-5) M) but hexamethonium (2 x 10(-4) M) significantly altered the response only to DMPP. 4. Physostigmine (10(-5) M) shifted the ACh response curve to the left but physostigmine itself caused inhibition of Jsm which was blocked by atropine. 5. Substitution of mucosal Cl- by NO3- reduced Jsm to a similar extent to maximum cholinoceptor effect and abolished responses to bethanecol. Anoxia further reduced Jsm in the presence of NO3-. 6. Mucosal SITS and DIDS (1 mM) reduced Jsm but this was less than the maximum inhibition seen with drugs acting on cholinoceptors or mucosal Cl- removal. Serosal DIDS caused a similar inhibition. 7. We conclude that cholinoceptor agonists inhibit but do not abolish luminal bicarbonate transport by an action on muscarinic receptors.