Histamine H₃ receptor-mediated suppression of inhibitory synaptic transmission in the submucous plexus of guinea-pig small intestine

Conventional intracellular microelectrodes and marker injection techniques were used to study the actions of histamine on inhibitory synaptic transmission in the submucous plexus of guinea-pig small intestine. Bath application of histamine (1-300 μM) reversibly suppressed both noradrenergic and non-adrenergic slow inhibitory postsynaptic potentials in a concentration-dependent manner. These effects of histamine were mimicked by the selective histamine H₃ receptor agonist R(-)-α-methylhistamine but not the selective histamine H₁ receptor agonist, 6-[2-(4-imidazolyl)ethylamino]-N-(4-trifluoromethylphenyl) heptanecarboxamide (HTMT dimaleate), or the selective histamine H₂ receptor agonist, dimaprit. The histamine H₃ receptor antagonist, thioperamide, blocked the effects of histamine. Histamine H₁ and H₂ receptor antagonists did not change the action of histamine. Hyperpolarizing responses to focal application of norepinephrine or somatostatin by pressure ejection from micropipettes were unaffected by histamine and R(-)-α-methylhistamine. The results suggest that histamine acts at presynaptic histamine H₃ receptors on the terminals of sympathetic postganglionic fibers and intrinsic somatostatinergic nerves in the small intestine to suppress the release of the inhibitory neurotransmitters, norepinephrine and somatostatin. (C) 2000 Elsevier Science B.V.