Histamine-induced ion secretion across rat distal colon: Involvement of histamine H 1 and H 2 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.