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Synaptic vesicular monoamine transporter expression: distribution and pharmacologic profile
A M Gonzalez1, D Walther, A Pazos
1Molecular Neurobiology Branch, National Institute on Drug Abuse, Addiction Research Center, Baltimore, MD 21224.
Brain Research. Molecular Brain Research
|March 1, 1994
Summary
The human vesicular monoamine transporter (hSVMT) is a protein crucial for packaging monoamine transmitters. Studies reveal its expression in specific brain regions and its pharmacological profile, highlighting its role in histamine and neurotransmitter transport.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- The human vesicular monoamine transporter (hSVMT) is a protein involved in neurotransmitter transport.
- Understanding its distribution and pharmacological properties is key to elucidating its physiological roles.
Purpose of the Study:
- To characterize the human vesicular monoamine transporter (hSVMT) at the molecular and functional level.
- To investigate the expression patterns and binding affinities of hSVMT.
Main Methods:
- cDNA analysis to predict protein structure.
- Northern blot analysis to determine mRNA expression.
- In situ hybridization to localize SVMT expression in neural tissues.
- COS cell expression and radioligand binding assays to determine transporter affinities.
Main Results:
- hSVMT cDNA predicts a 515-amino acid protein with 92% identity to rat SVMT.
- SVMT mRNAs are expressed in specific regions of the human and rat brain, including the hypothalamus and brainstem.
- In situ hybridization shows SVMT expression in human substantia nigra compacta and rat hypothalamic neurons.
- hSVMT exhibits high affinity for tetrabenazine and reserpine, with lower affinities for other monoamines and psychotropic drugs.
Conclusions:
- The findings extend the pharmacological characterization and distribution studies of hSVMT.
- SVMT likely plays a physiological role in packaging monoamine transmitters, including histamine.