Synaptic vesicular monoamine transporter expression: distribution and pharmacologic profile.
The human vesicular monoamine transporter (hSVMT) cDNA predicts a protein of 515 amino acids that shares 92% amino acid identity with the rat cDNA. Northern analyses reveal expression of 4.3 kb SVMT mRNAs in rat hypothalamus, midbrain and brainstem, a 3 kb hSVMT mRNA in human brainstem and a 4.8 kb hSVMT mRNA in human hypothalamus. In situ hybridization documents significant SVMT expression in human nigra compacta neurons and in rat hypothalamic neurons whose distribution patterns are identical to those previously reported to display histaminergic markers. COS cell hSVMT expression yielded nanomolar affinities for tetrabenazine and reserpine, micromolar affinities for haloperidol, GBR12909, serotonin, mazindol, nomifensin and d-amphetamine, while dopamine, epinephrine, norepinephrine and histamine each displayed millimolar affinities. These observations extend the pharmacological characterization of hSVMT and studies of its distribution, and indicate likely physiological roles for SVMT in packaging monoamine transmitters including histamine.
Gonzalez
A M
AM
Molecular Neurobiology Branch, National Institute on Drug Abuse, Addiction Research Center, Baltimore, MD 21224.
Walther
D
D
Pazos
A
A
Uhl
G R
GR
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D001933:Brain Stem / Q000737:chemistry; D006023:Glycoproteins / Q000032:analysis* / Q000096:biosynthesis; D006801:Humans; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents / Q000032:analysis* / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis*; D011869:Radioligand Assay; D051381:Rats; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins
D006023:Glycoproteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D012333:RNA, Messenger; D050492:Vesicular Biogenic Amine Transport Proteins; D050493:Vesicular Monoamine Transport Proteins