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Muscarinic M2 Stimulation Releases Histamine in the Totally Isolated, Vascularly Perfused Rat Stomach

1988; Taylor & Francis; Volume: 23; Issue: 9 Linguagem: Inglês

10.3109/00365528809090168

1502-7708

Arne K. Sandvik, P. M. Kleveland, Helge L. Waldum,

Asthma and respiratory diseases

AbstractThe present study examines the role of histamine in the stimulation of acid secretion induced by vagal nerve stimulation and by the muscarinic Ml 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 Mi-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 μmol/60 min (mean ± SEM). The Ml antagonist pirenzepine and the M1/M2 antagonist atropine both significantly (p < 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.Key Words: Gastric acidhistamineisolated rat stomachmuscarinic Ml agonistnerve stimulation