Histamine H-3 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 transmis sion in the submucous plexus of guinea-pig small intestine. Bath applicatio n of histamine (1-300 mu M) reversibly suppressed both noradrenergic and no n-adrenergic slow inhibitory postsynaptic potentials in a concentration-dep endent manner. These effects of histamine were mimicked by the selective hi stamine H-3 receptor agonist R(-)-alpha-methylhistamine but not the selecti ve histamine H-1 receptor agonist, 6-[2-(4-imidazolyl)ethylamino]-N-(4-trif luoromethylphenyl) heptanecarboxamide (HTMT dimaleate), or the selective hi stamine H-2 receptor agonist, dimaprit. The histamine H-3 receptor antagoni st, thioperamide, blocked the effects of histamine. Histamine H-1 and H-2 r eceptor antagonists did not change the action of histamine. Hyperpolarizing responses to focal application of norepinephrine or somatostatin by pressu re ejection from micropipettes were unaffected by histamine and R(-)-alpha- methyl-histamine. The results suggest that histamine acts at presynaptic hi stamine H-3 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 somatos tatin. (C) 2000 Elsevier Science B.V. All rights reserved.