| Description: | The histamine receptor H3 (HRH3) is a presynaptic autoreceptor on histamine neurons in the brain and a presynaptic heteroreceptor in nonhistamine-containing neurons in both the central and peripheral nervous systems. The deduced 445-amino acid HRH3 protein contains 7 predicted transmembrane domains. HRH3 has significant sequence homology to members of the biogenic amine subfamily of GPCRs. Most notable is an aspartic acid residue in the predicted third transmembrane domain, which is a hallmark of the biogenic amine receptor subfamily; this residue is the putative binding site for the primary amine. HRH3 shares 22% and 21.4% amino acid sequence homology with the H1 and H2 receptors, respectively. Expression of recombinant HRH3 in a variety of cell lines conferred an ability to inhibit adenylate cyclase in response to histamine, but not to acetylcholine or any other biogenic amine. Northern blot analysis of human tissues showed HRH3 expression only in the brain, with highest expression in the thalamus and caudate nucleus. Whereas Northern blot analysis did not detect HRH3 expression in any peripheral tissue examined, RT-PCR showed expression in human small intestine, testis, and prostate. In situ hybridization of rat brain sections showed that Hrh3 is abundantly expressed in brain. Hrh3 was most notably observed throughout the thalamus, the ventromedial hypothalamus, and the caudate nucleus. Strong expression was also seen in layers II, V, and VIb of the cerebral cortex, in the pyramidal layers of the hippocampus, and in olfactory tubercle. In addition, Hrh3 expression was found in the locus ceruleus and in the histaminergic cell bodies in the tuberomammillary nuclei. |
