title: Modulation of noradrenaline release in rat isolated stomach by prostanoids, but not by histaminergic mechanisms.
abstract: Several gastric functions are modulated by the sympathetic nervous system, but local mechanisms involved in the control of noradrenaline release are largely unknown. Overflow of endogenous noradrenaline was studied from isolated rat stomach incubated in Ussing chambers allowing the separate determination of mucosal and serosal overflow. Spontaneous noradrenaline overflow was similar at the mucosal and serosal side, but electrical field stimulation caused a frequency-dependent increase in noradrenaline overflow selectively at the serosal side. Evoked noradrenaline overflow was blocked by tetrodotoxin, not affected by indometacin and markedly enhanced (by about 250%) by yohimbine. In the presence of indometacin and yohimbine, sulprostone (an agonist at EP1/EP3 receptors) and misoprostol (an agonist at EP2/EP3 receptors) reduced the noradrenaline overflow evoked by stimulation at 3 Hz maximally by about 80% (EC50: 6 nmol/l and 11 nmol/l, respectively). The EP1 receptor selective antagonist AH 6809 (6-isopropoxy-9-oxoxanthene-2-carboxylic acid) did not antagonize the inhibition by sulprostone. Noradrenaline overflow evoked by stimulation at 1 Hz and 3 Hz was increased by scopolamine by about 50% and almost completely inhibited by oxotremorine. Neither, histamine nor the H3 receptor selective agonist (R)-alpha-methyl-histamine, nor the H1, H2 and H3 selective receptor antagonists mepyramine, cimetidine and thioperamide significantly affected noradrenaline overflow evoked by stimulation at 1 Hz or 3 Hz. In conclusion, impulse-induced noradrenaline release in the rat stomach is controlled by multiple presynaptic mechanisms involving alpha 2-adrenergic autoreceptors, EP3 prostanoid and muscarine heteroreceptors, whereas histaminergic mechanisms do not appear to be significant.
authors.affiliation: Department of Pharmacology, University of Frankfurt, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Racké
authors.forename: L
authors.initials: L
authors.lastname: Berrino
authors.forename: A
authors.initials: A
authors.lastname: Möhlig
authors.forename: R
authors.initials: R
authors.lastname: Jäger
authors.forename: I
authors.initials: I
authors.lastname: Griepenkerl
authors.forename: M
authors.initials: M
authors.lastname: Bräutigam
authors.forename: A
authors.initials: A
authors.lastname: Reimann
mesh_terms: D000020:Abortifacient Agents, Nonsteroidal / Q000494:pharmacology*; D000818:Animals; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D017442:Histamine Agonists / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008761:Methylhistamines / Q000494:pharmacology; D016595:Misoprostol / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D010095:Oxotremorine / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D011968:Receptors, Histamine / Q000187:drug effects* / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000187:drug effects*; D012601:Scopolamine / Q000494:pharmacology; D013270:Stomach / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D014966:Xanthenes / Q000494:pharmacology; D044004:Xanthones; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000020:Abortifacient Agents, Nonsteroidal; D017442:Histamine Agonists; D008761:Methylhistamines; D018721:Muscarinic Agonists; D010276:Parasympatholytics; D018341:Receptors, Adrenergic, alpha-2; D011968:Receptors, Histamine; D011982:Receptors, Prostaglandin; D014966:Xanthenes; D044004:Xanthones; D016595:Misoprostol; D015016:Yohimbine; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; D013779:Tetrodotoxin; C016767:sulprostone; D010095:Oxotremorine; C069357:alpha-methylhistamine; D012601:Scopolamine; D015232:Dinoprostone; D009638:Norepinephrine; D007213:Indomethacin