title: Histamine-induced ion secretion across rat distal colon: involvement of histamine H1 and H2 receptors.
abstract: The aim of the present study was to investigate the effect of histamine, a product of e.g. mast cells, on short-circuit current (I(sc)) across rat distal colon. Histamine concentration-dependently stimulated an increase in I(sc), which often was preceded by a transient negative current. Neither a release of neurotransmitters nor a release of prostaglandins contributed to the histamine response. The histamine-induced increase in I(sc) was blocked by the histamine H(1) antagonist, pyrilamine, but was resistant against the histamine H(2) antagonist, cimetidine. Conversely, the histamine H(1) agonist, TMPH (2-(3-trifluoromethylphenyl)histamine), exclusively evoked an increase in I(sc), whereas the histamine H(2) agonist, amthamine, evoked only a decrease in I(sc) suggesting that stimulation of different types of histamine receptors is responsible for the two phases of the response evoked by native histamine. Histamine induces the opening of glibenclamide-sensitive Cl(-) channels and of charybdotoxin-sensitive K(+) channels in the apical membrane as demonstrated by experiments at basolaterally depolarized epithelia. A further action site is the basolateral membrane, because histamine stimulates a charybdotoxin- and tetrapentylammonium-sensitive K(+) conductance in this membrane as observed in tissues, in which the apical membrane was permeabilized with an ionophore, nystatin. The increase in I(sc) evoked by histamine was blocked after depletion of intracellular Ca(2+) stores with cyclopiazonic acid and after blockade of inositol 1,4,5-trisphosphate (IP(3)) receptors, suggesting a release of stored Ca(2+). This was confirmed by the observation that the histamine H(1) agonist TMPH induced an increase in the fura-2 ratio signal of epithelial cells within isolated colonic crypts. Consequently, the mediator histamine seems to stimulate both histamine H(1) and H(2) receptors, from which the former seems to be prominently involved in the induction of epithelial chloride secretion.
authors.affiliation: Institut für Veterinär-Physiologie, Justus-Liebig-Universität Giessen, Frankfurter Str. 100, D-35392 Giessen, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schultheiss
authors.forename: Britta
authors.initials: B
authors.lastname: Hennig
authors.forename: Walter
authors.initials: W
authors.lastname: Schunack
authors.forename: Gundula
authors.initials: G
authors.lastname: Prinz
authors.forename: Martin
authors.initials: M
authors.lastname: Diener
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D002712:Chlorides / Q000378:metabolism*; D003106:Colon / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011969:Receptors, Histamine H1 / Q000032:analysis / Q000187:drug effects*; D011970:Receptors, Histamine H2 / Q000032:analysis / Q000187:drug effects*; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D002712:Chlorides; D017442:Histamine Agonists; D006633:Histamine Antagonists; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D019837:Ryanodine Receptor Calcium Release Channel; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D006632:Histamine; D000242:Cyclic AMP; D011188:Potassium; D002118:Calcium