Actions of histamine on muscle and ganglia of the guinea pig gallbladder

Jason M. Hemming, Fay A. Guarraci, Tracy A. Firth, Lee J. Jennings, Mark T. Nelson, Gary M. Mawe

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Histamine is an inflammatory mediator present in mast cells, which are abundant in the wall of the gallbladder. We examined the electrical properties of gallbladder smooth muscle and nerve associated with histamine-induced changes in gallbladder tone. Recordings were made from gallbladder smooth muscle and neurons, and responses to histamine and receptor subtype-specific compounds were tested. Histamine application to intact smooth muscle produced a concentration-dependent membrane depolarization and increased excitability. In the presence of the H2 antagonist ranitidine, the response to histamine was potentiated. Activation of H2 receptors caused membrane hyperpolarization and elimination of spontaneous action potentials. The H2 response was attenuated by the ATP-sensitive K+ (K(ATP)) channel blocker glibenclamide in intact and isolated smooth muscle. Histamine had no effect on the resting membrane potential or excitability of gallbladder neurons. Furthermore, neither histamine nor the H3 agonist R-α-methylhistamine altered the amplitude of the fast excitatory postsynaptic potential in gallbladder ganglia. The mast cell degranulator compound 48/80 caused a smooth muscle depolarization that was inhibited by the H1 antagonist mepyramine, indicating that histamine released from mast cells can activate gallbladder smooth muscle. In conclusion, histamine released from mast cells can act on gallbladder smooth muscle, but not in ganglia. The depolarization and associated contraction of gallbladder smooth muscle represent the net effect of activation of both H1 (excitatory) and H2 (inhibitory) receptors, with the H2 receptor-mediated response involving the activation of K(ATP) channels.
    Original languageEnglish
    Pages (from-to)G622-G630
    JournalAJP: Gastrointestinal and Liver Physiology
    Volume279
    Issue number3
    Publication statusPublished - 2000

    Keywords

    • ATP-sensitive K+ channel
    • Cholecystitis
    • Compound 48/80
    • Innervation
    • Mast cell
    • Motility

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