title: Muscarinic M2 stimulation releases histamine in the totally isolated, vascularly perfused rat stomach.
abstract: The present study examines the role of histamine in the stimulation of acid secretion induced by vagal nerve stimulation and by the muscarinic M1 agonist McN-A-343 in the totally isolated, vascularly perfused rat stomach. The stimuli were combined with an agent stimulating the cAMP system (isobutyl methylxanthine (IMX) or forskolin), a muscarinic antagonist (atropine or pirenzepine), or a histamine H2 antagonist (ranitidine). IMX and forskolin potentiated McN-A-343-stimulated acid secretion, yielding acid outputs of 280% and 260% of the sum of McN-A-343- and IMX-, or McN-A-343- and forskolin-stimulated outputs, respectively. Ranitidine inhibited acid secretion stimulated by McN-A-343 alone or in combination with IMX, whereas the forskolin-stimulated secretion was not influenced by the H2 antagonist. This strongly indicates that endogenous histamine potentiates muscarinic M1-stimulated acid secretion by increasing parietal cell cAMP. Vagal nerve stimulation with IMX increased acid output from 12.2 +/- 3.0 to 49.2 +/- 9.3 mumol/60 min (mean +/- SEM). The M1 antagonist pirenzepine and the M1/M2 antagonist atropine both significantly (p less than 0.01) inhibited vagally stimulated acid secretion. Histamine output as measured in the venous effluent was unchanged by McN-A-343, whereas nerve stimulation induced a clear increase in venous histamine output, from 101 +/- 21 before to 212 +/- 28 pmol/min (mean +/- SEM) after initiation of nerve stimulation. Histamine release was reduced to base-line levels by atropine but only insignificantly inhibited by pirenzepine, indicating a muscarinic M2 stimulation of histamine release in the rat stomach.
authors: Dept. of Medicine, Trondheim University, Norway.
authors: A K
authors: AK
authors: Sandvik
authors: P M
authors: PM
authors: Kleveland
authors: H L
authors: HL
authors: Waldum
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D004558:Electric Stimulation; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D006636:Histamine Release / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*; D014630:Vagus Nerve / Q000502:physiology
chemical_list: D011976:Receptors, Muscarinic; D005576:Colforsin; D015056:1-Methyl-3-isobutylxanthine