A search for presynaptic inhibitory histamine receptors in guinea-pig tissues: Further H-3 receptors but no evidence for H-4 receptors

摘要

The histamine H-4 receptor is coupled to G(i/o) proteins and expressed on inflammatory cells and lymphoid tissues; it was suggested that this receptor also occurs in the brain or on peripheral neurones. Since many G(i/)o protein-coupled receptors, including the H-3 receptor, serve as presynaptic inhibitory receptors, we studied whether the sympathetic neurones supplying four peripheral tissues and the cholinergic neurones in the hippocampus from the guinea-pig are equipped with release-modulating H-4 and H-3 receptors. For this purpose, we preincubated tissue pieces from the aorta, atrium, renal cortex and vas deferens with H-3-noradrenaline and hippocampal slices with H-3-choline and determined the electrically evoked tritium overflow. The stimulation-evoked overflow in the five superfused tissues was inhibited by the muscarinic receptor agonist oxotremorine, which served as a positive control, but not affected by the H-4 receptor agonist 4-methylhistamine. The H-3 receptor agonist R-alpha-methylhistamine inhibited noradrenaline release in the peripheral tissues without affecting acetylcholine release in the hippocampal slices. Thioperamide shifted the concentration-response curve of histamine in the aorta and the renal cortex to the right, yielding apparent pA2 values of 8.0 and 8.1, respectively, which are close to its affinity at other H-3 receptors but higher by one log unit than its pK(i) at the H-4 receptor of the guinea-pig. In conclusion, histamine H-4 receptors could not be identified in five experimental models of the guineapig that are suited for the detection of presynaptic inhibitory receptors whereas H-3 receptors could be shown in the peripheral tissues but not in the hippocampus. This article is part of the Special Issue entitled 'Histamine Receptors'. (C) 2015 Elsevier Ltd. All rights reserved.