Cloning and expression of the mouse histamine H3 receptor: evidence for multiple isoforms.
The existence of mouse H3-receptor isoforms was investigated by PCR analysis and cDNA cloning. Splicing mechanisms previously reported in various species are conserved in the mouse. The retention/deletion of a fragment in the third intracellular loop of the mouse receptor leads to the existence of three isoforms designated mH(3(445)), mH(3(413)) and mH(3(397)) according to the length of their deduced amino acid sequence. PCR analysis showed that mouse H3-receptor isoforms display different expression patterns in the brain. Following expression in Cos-1 cells, [125I]iodoproxyfan binding indicated similar pharmacological profiles of the mH(3(445)), mH(3(413)) and mH(3(397)) isoforms. The pharmacological profile of the mouse H3 receptor is more similar to the rat receptor than to the human receptor, although some differences were also observed between the mouse and rat receptors. For example, the potency of thioperamide and ciproxifan is slightly higher at the mouse receptor than at the rat receptor but 40-100-fold higher than at the human receptor. In situ hybridization histochemistry showed that the distribution of H3-receptor mRNAs in the mouse brain is rather similar to that previously reported in the rat brain. However, the autoradiographic and cellular expression patterns observed in several brain areas such as the thalamus or hippocampus reveal important differences between the two species.
Rouleau
Agnès
A
Unité de Neurobiologie et Pharmacologie Moléculaire (U573) de l'INSERM, Centre Paul Broca, Paris, France.
Héron
Anne
A
Cochois
Véronique
V
Pillot
Catherine
C
Schwartz
Jean-Charles
JC
Arrang
Jean-Michel
JM
D000818:Animals; D015152:Blotting, Northern / Q000379:methods; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D003164:Competitive Bidding / Q000379:methods; D015870:Gene Expression / Q000502:physiology*; D006632:Histamine / Q000493:pharmacokinetics; D017442:Histamine Agonists / Q000493:pharmacokinetics; D006633:Histamine Antagonists / Q000493:pharmacokinetics; D007093:Imidazoles / Q000493:pharmacokinetics; D017403:In Situ Hybridization / Q000379:methods; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D010880:Piperidines / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011869:Radioligand Assay / Q000379:methods; D051381:Rats; D018100:Receptors, Histamine H3 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013890:Thiourea / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014162:Transfection / Q000379:methods
D017442:Histamine Agonists; D006633:Histamine Antagonists; D007093:Imidazoles; D007457:Iodine Radioisotopes; D007527:Isoenzymes; D010880:Piperidines; D012333:RNA, Messenger; D018100:Receptors, Histamine H3; C090115:iodoproxyfan; C077430:imetit; D006632:Histamine; D013890:Thiourea; C052075:thioperamide