RGD Reference Report - Cloning of rat histamine H(3) receptor reveals distinct species pharmacological profiles. - Rat Genome Database

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Cloning of rat histamine H(3) receptor reveals distinct species pharmacological profiles.

Authors: Lovenberg, TW  Pyati, J  Chang, H  Wilson, SJ  Erlander, MG 
Citation: Lovenberg TW, etal., J Pharmacol Exp Ther 2000 Jun;293(3):771-8.
RGD ID: 632981
Pubmed: PMID:10869375   (View Abstract at PubMed)

The recent cloning and characterization of the human histamine H(3) receptor cDNA marked a significant step toward a greater understanding of the role of this receptor in the central nervous system. We now report the cloning of the rat histamine H(3) receptor cDNA and demonstrate distinct pharmacological species differences. The rat cDNA clone encodes a putative 445-amino acid protein with 93% identity to the human H(3) receptor. Northern blot analysis revealed a major single entity of 2.7-kb in length expressed only in brain. Transfection of the rat receptor cDNA into SK-N-MC cells conferred an ability to inhibit forskolin-stimulated cAMP formation in response to histamine and other H(3) agonists. N-[(3)H]methylhistamine saturably bound to transfected cells with high affinity (K(d) = 0.8 nM). All agonists tested had low or subnanomolar K(i) values similar to that for the human recombinant receptor. The antagonists thioperamide and clobenpropit also bound with high affinity (K(i) = 4 and 0.4 nM, respectively). This is in contrast to the antagonist profile obtained for the human recombinant receptor that showed K(i) values of 58 and 0.6 nM for thioperamide and clobenpropit, respectively. These data suggest that the low affinity of thioperamide for the human H(3) receptor represents a species difference in pharmacology and not a unique pharmacological subtype. It also was found that chloroproxyfan behaved as a full agonist at the rat recombinant receptor. These findings highlight the significance of validating the pharmacology of experimental compounds at both the rat and human H(3) receptors.

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
clozapine multiple interactionsISOHrh3 (Rattus norvegicus)632981; 632981Clozapine binds to Hrh3 protein and Clozapine inhibits the reaction [N-methylhistamine binds to Hrh3 protein]RGD 
clozapine multiple interactionsEXP 632981Clozapine binds to Hrh3 protein and Clozapine inhibits the reaction [N-methylhistamine binds to Hrh3 protein]RGD 
histamine multiple interactionsISOHrh3 (Rattus norvegicus)632981; 632981Histamine binds to Hrh3 protein and Histamine inhibits the reaction [N-methylhistamine binds to Hrh3 protein]RGD 
histamine multiple interactionsEXP 632981Histamine binds to Hrh3 protein and Histamine inhibits the reaction [N-methylhistamine binds to Hrh3 protein]RGD 
imetit multiple interactionsISOHrh3 (Rattus norvegicus)632981; 632981Imetit binds to Hrh3 protein and imetit inhibits the reaction [N-methylhistamine binds to Hrh3 protein]RGD 
imetit multiple interactionsEXP 632981Imetit binds to Hrh3 protein and imetit inhibits the reaction [N-methylhistamine binds to Hrh3 protein]RGD 
Immepip multiple interactionsISOHrh3 (Rattus norvegicus)632981; 632981Immepip binds to Hrh3 protein and Immepip inhibits the reaction [N-methylhistamine binds to Hrh3 protein]RGD 
Immepip multiple interactionsEXP 632981Immepip binds to Hrh3 protein and Immepip inhibits the reaction [N-methylhistamine binds to Hrh3 protein]RGD 
N(tele)-methylhistamine affects bindingISOHrh3 (Rattus norvegicus)632981; 632981N(tele)-methylhistamine binds to Hrh3 proteinRGD 
N(tele)-methylhistamine affects bindingEXP 632981N(tele)-methylhistamine binds to Hrh3 proteinRGD 
Thioperamide multiple interactionsISOHrh3 (Rattus norvegicus)632981; 632981Thioperamide binds to Hrh3 protein and Thioperamide inhibits the reaction [N-methylhistamine binds to Hrh3 protein]RGD 
Thioperamide multiple interactionsEXP 632981Thioperamide binds to Hrh3 protein and Thioperamide inhibits the reaction [N-methylhistamine binds to Hrh3 protein]RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of adenylate cyclase activity  IDA 632981 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
amine binding  IPIThioperamide632981 RGD 
heterocyclic compound binding  IPIImmepip more ...632981 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hrh3  (histamine receptor H3)

Genes (Mus musculus)
Hrh3  (histamine receptor H3)

Genes (Homo sapiens)
HRH3  (histamine receptor H3)


Additional Information