The secretory actions of histamine in rat small intestine.

Abstract

SUMMARY1. Histamine caused a dose-dependent rise in the transintestinal potential difference in vivo that was competitively blocked by H1, but not by H2 antagonists. This effect of histamine was also reduced by the cyclo-oxygenase inhibitor indomethacin.2. Histamine induced a net secretion of fluid by the small intestine and this effect was reduced by indomethacin.3, In intestinal sheets histamine increased the potential difference, short-circuit current and tissue resistance. This response was decreased in the absence of Cl-and in the presence of furosemide, suggesting that Cl-secretion was responsible for the observed electrical changes. This was confirmed by direct measurement of ion fluxes which showed an increase in net Cl-secretion together with an inhibition of net Na+ absorption.4. The response to histamine was Ca2+-dependent since it was inhibited by removal of serosal Ca2+ and by verapamil.5. Indomethacin caused a dose-dependent reduction in the response of intestinal sheets to histamine, without affecting the rise in short-circuit current induced by mucosal glucose or serosal prostaglandin E2. Mepacrine also inhibited the response to histamine, but not that to prostaglandin E2.6. It is concluded that histamine induces intestinal secretion by stimulating the production of prostaglandins which then activate the secretory process.

Intestinal secretagogues increase cytosolic free Ca2+ concentration and K+ conductance in a human intestinal epithelial cell line

“…6A,B) strongly suggest that the origin of Ca 2+ ions mobilized upon stimulation with histamine is intracellular. This is in contrast to the observation that histamine-induced C1 secretion is inhibited by deprivation of serosal Ca 2+ ions or by the application of varapamil in rat small intestine (Hardcastle & Hardcastle, 1987), but in good agreement with the finding that histamine-induced Ca 2+ mobilization is not affected by deprivation of the extracellular Ca 2+ ions in colonic T84 cells (Wasserman et al, 1988). Since IP3 is known to provoke the Ca 2+ release from intracellular nonmitochondrial stores in permeabilized enterocytes (Velasco et al, 1986;Ilundain et al, 1987;van Coryen et al, 1987), histamine-induced responses might be mediated by IP3.…”

“…Two classes of membrane receptors may generally be distinguished: those coupled to phospholipase C, activation of which generates inositol trisphosphate (IP3) and diacylglycerol, thereby triggering the regulatory process mediated by Ca 2 § and protein kinase C (Nishizuka, 1984), and those to adenylate cyclase catalyzing the cyclic AMP production. In epithelial cells of the small intestine, the receptors of ACh, 5-HT and histamine may belong to the former class, since the action of these agonists are known to be mediated by cytosolic Ca 2+ ions (Bolton & Field, 1977;Hardcastle, Hardcastle & Redfern, 1981;Chang et al, 1986;Donowitz & Welsh, 1987;Hardcastle & Hardcastle, 1987). On the other hand, VIP, secretin and ATP may be the agonists for the latter class, since an increase in the cellular cyclic AMP or activation of adenylate cyclase was observed in enterocytes upon stimulation with these secretagogues (Schwartz et al, 1974;Klaeveman et al, 1975;Laburthe et al, 1979a,b;Binder et al, 1980;Korman et al, 1982;Dharmsathaphorn et al, 1983).…”

Chloride conductance and genetic background modulate the cystic fibrosis phenotype of ΔF508 homozygous twins and siblings

“…2.10 -4 mol/l, M), to inhibit DIDS-sensitive Cl -transporters like the Ca 2+ -dependent Cl -channels (14,15) and the ORCC (39); and (f) histamine (5.10 -4 mol/l, S), to reactivate the Ca 2+ -dependent Cl -secretory pathway (40). Two rectal biopsies were obtained for every patient participating in the IC measurements.…”

Stimulation of chloride secretion by N‐formyl‐methionylleucylphenylalanine (FMLP) in rabbit ileal mucosa.

“…Following serosal but not mucosal addition, FMLP elicits a transient increase in 'sc and Gt with a maximal effect occurring within 2-3 min and returning to baseline within 10 min. Similar time courses have been seen with other secretagogues such as LTD4, bradykinin, histamine and carbachol (Tapper, Powell & Morris, 1978;Manning, Synder, Kachur, Miller & Field, 1982;Musch et al 1983;Hardcastle & Hardcastle, 1987;Smith et al 1988b). Pre-treatment of the ileum with a maximal concentration of FMLP sensitizes the tissue to subsequent stimulation similar to previous results reported for LTD4,arachidonic acid and prostaglandins in the rat and rabbit ileum (Field et al 1981;Smith et al 1988b).…”