Localization of the histamine H2 receptor and gene transcripts in rat stomach: back to parietal cells.

Unité de Neurobiologie et Pharmacologie (U. 109) de l'INSERM, Centre Paul Broca, Paris, France.
Biochemical and Biophysical Research Communications (Impact Factor: 2.28). 03/1994; 198(3):1195-202. DOI: 10.1006/bbrc.1994.1169
Source: PubMed

ABSTRACT In contrast with many physiological studies suggesting that histamine H2 receptors are present on acid-secreting parietal cells of the gastric epithelium, it was recently shown that immune cells in the lamina propria are the only cells expressing H2-receptor mRNAs (Mezey and Palkovits, Science, 1992, 258, 1662-1665). We have reinvestigated the cellular localization of H2 receptors in the rat stomach by visualizing both the H2 receptor mRNA and the H2-receptor protein itself. In situ hybridization histochemistry performed with an antisense riboprobe for the rat H2 receptor, and autoradiographic distribution of 125I-aminopotentidine binding sites, a highly selective H2-receptor ligand, did not show any labeling of the lamina propria. Signals were clearly and solely detected in the gastric epithelium, the strongest being observed in the upper part of the glands where the H2 receptor gene transcripts were only detected within parietal cells. In situ hybridization performed with an antisense riboprobe for L-histidine decarboxylase mRNA confirmed the basal localization of the histamine-synthetizing cells in the rat gastric gland, at some distance from parietal histamine-sensitive cells.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Orange et al reported an allelic variant of the human histamine H2 receptor, in which adenine 649 was replaced with guanine, to be more frequent in the schizophrenic population than controls in British Caucasians. The A649 to G change causes an Asn to Asp transition at amino acid position 217 in the third intracellular region, which is postulated to be important for receptor function. Herein, we analyzed the functional significance of this variant using wild-type and variant receptors expressed in Chinese hamster ovary cells. The variant receptor was associated with markedly lower basal cAMP productions than the wild-type receptor. Histamine-dependent cAMP productions via the variant receptor were lower as well. Treatment of cells expressing variant receptors with 10(-5) M ranitidine for 24 h resulted in a reduced degree of receptor upregulation as compared with the wild-type receptor. Thus, this is the first report of an allelic variant of the human H2 receptor which confers altered receptor function. To analyze gastric acid secretion in individuals with this variant, we examined 100 Japanese control subjects. However, neither heterozygotes nor homozygotes were found, suggesting that this variant, if present, is uncommon in the Japanese population.
    The Pharmacogenomics Journal 02/2001; 1(1):78-83. · 5.13 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study was designed to examine the effects of histamine on gastric motility and its specific receptor in the circular smooth muscle of the human gastric corpus. Histamine mainly produced tonic relaxation in a concentration-dependent and reversible manner, although histamine enhanced contractility in a minor portion of tissues tested. Histamine-induced tonic relaxation was nerve-insensitive because pretreatment with nerve blockers cocktail (NBC) did not inhibit relaxation. Additionally, K(+) channel blockers, such as tetraethylammonium (TEA), apamin (APA), and glibenclamide (Glib), had no effect. However, N(G)-nitro-L-arginine methyl ester (L-NAME) and 1H-(1,2,4)oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC), did inhibit histamine-induced tonic relaxation. In particular, histamine-induced tonic relaxation was converted to tonic contraction by pretreatment with L-NAME. Ranitidine, the H2 receptor blocker, inhibited histamine-induced tonic relaxation. These findings suggest that histamine produced relaxation in circular smooth muscle of human gastric smooth muscle through H2 receptor and NO/sGC pathways.
    10/2014; 18(5):425-30.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: The histamine H3 receptor has been shown to inhibit pentagastrin-induced gastric acid secretion in dogs. Since pentagastrin releases histamine in dogs, we have now assessed whether the effects of H3-receptor ligands may be indirectly mediated by changes in gastric histamine release. METHODS: Pentagastrin infusions (1 or 6 micrograms/kg/h), alone or together with the H3-receptor agonist (R) alpha-methylhistamine (1.2 mumol/kg/h) or the antagonist thioperamide (0.1 mumol/kg/h), were performed in dogs. One group (anaesthetized) was used for enzyme immunoassays of plasma histamine and, when required. (R) alpha-methylhistamine in the gastrosplenic vein, and another group (non-anaesthetized) for measurement of gastric acid secretion. RESULTS: Histamine levels were increased five- and eight-fold after 1 and 6 micrograms/kg/h pentagastrin, respectively, whereas acid output was nearly maximal at the lower dosage. (R) alpha-methylhistamine, at a plasma concentration of 0.15 microM, inhibited histamine release by 78% (P < 0.007) and 37% (not significant) and the total acid output by 44% (P < 0.05) and 19% (not significant) after infusion of 1 and 6 micrograms/kg/h pentagastrin, respectively. Thioperamide, together with pentagastrin in low dose, significantly increased histamine release by 212% (P < 0.05), whereas acid output increased by 34% (not significant). CONCLUSIONS: The histamine H3 receptor mediates a negative feedback control of pentagastrin-induced release of gastric histamine. It is tonically activated by endogenous histamine after pentagastrin in low dosage. The control of acid secretion by the H3 receptor seems to involve modulation of endogenous histamine release, possibly by means of enterochromaffin-like cells.
    Scandinavian Journal of Gastroenterology 01/1996; 31(7):631-8. · 2.33 Impact Factor