The expression of mRNA for a kappa opioid receptor in the substantia nigra of Parkinson's disease brain

Mitsuhiko Yamada; Karen Groshan; Chan Tran Phung; Misa Yamada; Takashi Hisamitsu; Elliott Richelson

doi:10.1016/S0169-328X(96)00139-8

The expression of mRNA for a kappa opioid receptor in the substantia nigra of Parkinson's disease brain

Mitsuhiko Yamada, Karen Groshan, Chan Tran Phung, Misa Yamada, Takashi Hisamitsu, Elliott Richelson

Neuroscience

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

We molecularly cloned the kappa opioid receptor from a human substantia nigra cDNA library. When expressed in HEK293 cells, the cloned receptor had similar pharmacological characteristics to the rat kappa opioid receptor. Northern blot analysis showed the presence of a single transcript of about 6 kb in size for mRNA prepared from the substantia nigra. Using in situ hybridization histochemistry, we studied the expression of this receptor in postmortem human brains from control and Parkinson's disease subjects. Kappa opioid receptor mRNA was present in melanized (possibly dopaminergic) neurons of the substantia nigra and the nucleus paranigralis. On the other hand, Parkinson's disease brains had markedly fewer melanized neurons, as expected, and correspondingly very low or background levels of mRNA for the kappa opioid receptor. However, in some cases, remaining melanized neurons still expressed the receptor mRNA. From these results we suggest that dopaminergic neurons in the human substantia nigra and the nucleus paranigralis synthesize kappa opioid receptors and express them in their perikarya and their terminal regions. The kappa opioid receptor expressed in the melanized neurons may play a role in the normal function of dopaminergic systems and possibly in the etiology of Parkinson's disease.

Original language	English (US)
Pages (from-to)	12-20
Number of pages	9
Journal	Molecular Brain Research
Volume	44
Issue number	1
DOIs	https://doi.org/10.1016/S0169-328X(96)00139-8
State	Published - Feb 1997

Keywords

Aging
Dopamine
Human
Melanin
Molecular cloning
Transfection

ASJC Scopus subject areas

Molecular Biology
Cellular and Molecular Neuroscience

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10.1016/S0169-328X(96)00139-8

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title = "The expression of mRNA for a kappa opioid receptor in the substantia nigra of Parkinson's disease brain",

abstract = "We molecularly cloned the kappa opioid receptor from a human substantia nigra cDNA library. When expressed in HEK293 cells, the cloned receptor had similar pharmacological characteristics to the rat kappa opioid receptor. Northern blot analysis showed the presence of a single transcript of about 6 kb in size for mRNA prepared from the substantia nigra. Using in situ hybridization histochemistry, we studied the expression of this receptor in postmortem human brains from control and Parkinson's disease subjects. Kappa opioid receptor mRNA was present in melanized (possibly dopaminergic) neurons of the substantia nigra and the nucleus paranigralis. On the other hand, Parkinson's disease brains had markedly fewer melanized neurons, as expected, and correspondingly very low or background levels of mRNA for the kappa opioid receptor. However, in some cases, remaining melanized neurons still expressed the receptor mRNA. From these results we suggest that dopaminergic neurons in the human substantia nigra and the nucleus paranigralis synthesize kappa opioid receptors and express them in their perikarya and their terminal regions. The kappa opioid receptor expressed in the melanized neurons may play a role in the normal function of dopaminergic systems and possibly in the etiology of Parkinson's disease.",

keywords = "Aging, Dopamine, Human, Melanin, Molecular cloning, Transfection",

author = "Mitsuhiko Yamada and Karen Groshan and Phung, {Chan Tran} and Misa Yamada and Takashi Hisamitsu and Elliott Richelson",

note = "Funding Information: The authors thank Dr. Wallace W. Tourtellotte from the National Neurological Research Specimen Bank and Dr. Edward D. Bird from the Brain Tissue Resource Center for kindly supplying the brain samples. The authors also thank Ms. Stephanie Martinez for helping to prepare the manuscript. This work was supported by the Mayo Foundation for Medical Education and Research, and the American Heart Association. ",

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AU - Hisamitsu, Takashi

AU - Richelson, Elliott

N1 - Funding Information: The authors thank Dr. Wallace W. Tourtellotte from the National Neurological Research Specimen Bank and Dr. Edward D. Bird from the Brain Tissue Resource Center for kindly supplying the brain samples. The authors also thank Ms. Stephanie Martinez for helping to prepare the manuscript. This work was supported by the Mayo Foundation for Medical Education and Research, and the American Heart Association.

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N2 - We molecularly cloned the kappa opioid receptor from a human substantia nigra cDNA library. When expressed in HEK293 cells, the cloned receptor had similar pharmacological characteristics to the rat kappa opioid receptor. Northern blot analysis showed the presence of a single transcript of about 6 kb in size for mRNA prepared from the substantia nigra. Using in situ hybridization histochemistry, we studied the expression of this receptor in postmortem human brains from control and Parkinson's disease subjects. Kappa opioid receptor mRNA was present in melanized (possibly dopaminergic) neurons of the substantia nigra and the nucleus paranigralis. On the other hand, Parkinson's disease brains had markedly fewer melanized neurons, as expected, and correspondingly very low or background levels of mRNA for the kappa opioid receptor. However, in some cases, remaining melanized neurons still expressed the receptor mRNA. From these results we suggest that dopaminergic neurons in the human substantia nigra and the nucleus paranigralis synthesize kappa opioid receptors and express them in their perikarya and their terminal regions. The kappa opioid receptor expressed in the melanized neurons may play a role in the normal function of dopaminergic systems and possibly in the etiology of Parkinson's disease.

AB - We molecularly cloned the kappa opioid receptor from a human substantia nigra cDNA library. When expressed in HEK293 cells, the cloned receptor had similar pharmacological characteristics to the rat kappa opioid receptor. Northern blot analysis showed the presence of a single transcript of about 6 kb in size for mRNA prepared from the substantia nigra. Using in situ hybridization histochemistry, we studied the expression of this receptor in postmortem human brains from control and Parkinson's disease subjects. Kappa opioid receptor mRNA was present in melanized (possibly dopaminergic) neurons of the substantia nigra and the nucleus paranigralis. On the other hand, Parkinson's disease brains had markedly fewer melanized neurons, as expected, and correspondingly very low or background levels of mRNA for the kappa opioid receptor. However, in some cases, remaining melanized neurons still expressed the receptor mRNA. From these results we suggest that dopaminergic neurons in the human substantia nigra and the nucleus paranigralis synthesize kappa opioid receptors and express them in their perikarya and their terminal regions. The kappa opioid receptor expressed in the melanized neurons may play a role in the normal function of dopaminergic systems and possibly in the etiology of Parkinson's disease.

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The expression of mRNA for a kappa opioid receptor in the substantia nigra of Parkinson's disease brain

Abstract

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