PMID- 10347254
OWN - NLM
STAT- MEDLINE
DCOM- 19990617
LR  - 20151119
IS  - 0026-895X (Print)
IS  - 0026-895X (Linking)
VI  - 55
IP  - 6
DP  - 1999 Jun
TI  - Cloning and functional expression of the human histamine H3 receptor.
PG  - 1101-7
AB  - Histamine regulates neurotransmitter release in the central and peripheral
      nervous systems through H3 presynaptic receptors. The existence of the histamine 
      H3 receptor was demonstrated pharmacologically 15 years ago, yet despite
      intensive efforts, its molecular identity has remained elusive. As part of a
      directed effort to discover novel G protein-coupled receptors through homology
      searching of expressed sequence tag databases, we identified a partial clone
      (GPCR97) that had significant homology to biogenic amine receptors. The GPCR97
      clone was used to probe a human thalamus library, which resulted in the isolation
      of a full-length clone encoding a putative G protein-coupled receptor. Homology
      analysis showed the highest similarity to M2 muscarinic acetylcholine receptors
      and overall low homology to all other biogenic amine receptors. Transfection of
      GPCR97 into a variety of cell lines conferred an ability to inhibit
      forskolin-stimulated cAMP formation in response to histamine, but not to
      acetylcholine or any other biogenic amine. Subsequent analysis revealed a
      pharmacological profile practically indistinguishable from that for the histamine
      H3 receptor. In situ hybridization in rat brain revealed high levels of mRNA in
      all neuronal systems (such as the cerebral cortex, the thalamus, and the caudate 
      nucleus) previously associated with H3 receptor function. Its widespread and
      abundant neuronal expression in the brain highlights the significance of
      histamine as a general neurotransmitter modulator. The availability of the human 
      H3 receptor cDNA should greatly aid in the development of chemical and biological
      reagents, allowing a greater appreciation of the role of histamine in brain
      function.
FAU - Lovenberg, T W
AU  - Lovenberg TW
AD  - R.W. Johnson Pharmaceutical Research Institute, San Diego, California, USA.
      tlovenbe@prius.jnj.com
FAU - Roland, B L
AU  - Roland BL
FAU - Wilson, S J
AU  - Wilson SJ
FAU - Jiang, X
AU  - Jiang X
FAU - Pyati, J
AU  - Pyati J
FAU - Huvar, A
AU  - Huvar A
FAU - Jackson, M R
AU  - Jackson MR
FAU - Erlander, M G
AU  - Erlander MG
LA  - eng
SI  - GENBANK/AF140538
PT  - Journal Article
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Adenylyl Cyclase Inhibitors)
RN  - 0 (DNA, Complementary)
RN  - 0 (Methylhistamines)
RN  - 0 (Receptors, Histamine H3)
RN  - 0 (Receptors, Neurotransmitter)
RN  - 10028-17-8 (Tritium)
RN  - 6986-90-9 (alpha-methylhistamine)
RN  - 820484N8I3 (Histamine)
RN  - EC 4.6.1.1 (Adenylyl Cyclases)
SB  - IM
MH  - Adenylyl Cyclase Inhibitors
MH  - Adenylyl Cyclases/metabolism
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding, Competitive
MH  - Cells, Cultured
MH  - Central Nervous System/metabolism
MH  - Cloning, Molecular
MH  - DNA, Complementary/analysis
MH  - Histamine/metabolism
MH  - Humans
MH  - Methylhistamines/metabolism
MH  - Molecular Sequence Data
MH  - Rats
MH  - Receptors, Histamine H3/biosynthesis/*genetics
MH  - Receptors, Neurotransmitter/biosynthesis/genetics
MH  - Sequence Homology, Amino Acid
MH  - Thymus Gland/physiology
MH  - Tritium
EDAT- 1999/05/29 00:00
MHDA- 1999/05/29 00:01
CRDT- 1999/05/29 00:00
PHST- 1999/05/29 00:00 [pubmed]
PHST- 1999/05/29 00:01 [medline]
PHST- 1999/05/29 00:00 [entrez]
PST - ppublish
SO  - Mol Pharmacol. 1999 Jun;55(6):1101-7.