title: Serosal application of Ba(2+) induces oscillatory chloride secretion via activation of submucosal cholinergic neurones in guinea-pig distal colon.
abstract: The enteric nervous system regulates ion and fluid secretion in the mammalian intestine at both resting and stimulated conditions. To determine the type and activation mechanism of neurones involved, mucosa-submucosa sheets isolated from guinea-pig distal colon were studied in vitro in Ussing chambers. Serosal addition of 0.5-1 mM barium (Ba(2+)), a potassium (K(+)) channel inhibitor, caused oscillatory increases in short-circuit current (I(sc)). Mean values of the size and frequency of I(sc) were 369.1 microA cm(-2) and 2.3 min(-1). The oscillatory I(sc) induced by the low concentrations of Ba(2+) was blocked by either higher concentrations of Ba(2+) (2-5 mM) or other K(+) channel inhibitors, such as tetraethylammonium (TEA) (1 mM) and quinine (20 mM). The Ba(2+)-induced oscillatory I(sc) was also inhibited by tetrodotoxin (TTX) and atropine. In a nominally Ca(2+) free solution plus serosal addition of 0.1 mM ethylene glycol-bis (beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA), a Ca(2+) chelator, the oscillatory I(sc) slowed and diminished. Further, the Ba(2+)-induced oscillatory I(sc) was partially inhibited by apical addition of 100 microM 5'-nitro-2-(3-phenylpropylamino)benzoic-acid (NPPB), a Cl(-) channel inhibitor, and completely disappeared in a low Cl(-) solution (11 mM) on both sides. On the other hand, application of either cimetidine, a histamine H(2) receptor antagonist, or hexamethonium, a nicotinic antagonist, to the serosal side did not affect the Ba(2+)-induced oscillatory I(sc). In conclusion, the Ba(2+)-induced oscillatory I(sc) is the transepithelial Cl(-) current which is stimulated by activation of cholinergic neurones in submucosal plexus of guinea-pig distal colon.
authors.affiliation: Department of Physiology, Kitasato University School of Medicine, Sagamihara, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nishikitani
authors.forename: A
authors.initials: A
authors.lastname: Kokubo
authors.forename: H
authors.initials: H
authors.lastname: Takemura
authors.forename: K
authors.initials: K
authors.lastname: Saigenji
authors.forename: K
authors.initials: K
authors.lastname: Kawahara
mesh_terms: D000818:Animals; D001464:Barium / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000502:physiology; D002927:Cimetidine / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D004553:Electric Conductivity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005730:Ganglionic Blockers / Q000494:pharmacology; D006168:Guinea Pigs; D018738:Hexamethonium / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D002712:Chlorides; D004791:Enzyme Inhibitors; D005730:Ganglionic Blockers; D026902:Potassium Channel Blockers; D014665:Vasodilator Agents; D001464:Barium; D014660:Vasoactive Intestinal Peptide; D018738:Hexamethonium; D002927:Cimetidine; D006632:Histamine; D011188:Potassium; D002118:Calcium