Summary
Activities of the two forms of catechol-O-methyltransferase (COMT), viz. the soluble (S-COMT) and the membrane-bound (MB-COMT), have been studied in the rat striatum to characterize their localization in relation to the nigrostriatal dopaminergic neurons. Selective unilateral nigrostriatal dopaminergic lesions were produced by an intranigral injection of 6-hydroxydopamine (6-OHDA; 8μg/site). 6-OHDA caused an extensive lesion of the dopaminergic neurons as revealed by non-detectable concentrations of dopamine in the striata of the lesioned sites. In spite of that neither S-COMT nor MB-COMT activities were altered in comparison with the intact control striata. The intrastriatal injection of kainic acid significantly increased S-COMT activity but to some extent decreased MB-COMT activity. Kainic acid did not alter the striatal concentration of dopamine.
These results suggest that both S-COMT and MB-COMT reside postsynaptically the nigrostriatal dopaminergic neurons. S-COMT seems to be found mainly in striatal glial cells, whereas striatal MB-COMT might be located both in postsynaptic neuronal and extraneuronal cells.
Similar content being viewed by others
References
Alberici M, Rodrigues de Lores Arnaiz G, De Robertis E (1965) Catechol-O-methyltransferase in nerve endings of rat brain. Life Sci 4: 1951–1960
Assicot M, Bohuon C (1971) Presence of two distinct catechol-O-methyl-transferase activities in red blood cells. Biochimie 53: 871–874
Borchardt RT, Cheng CF (1978) Purification and characterization of rat heart and brain catechol methyltransferase. Biochim Biophys Acta 522: 49–62
Borchardt RT, Cheng CF, Cooke PH, Crevelig C R (1974) The purification and kinetic properties of liver microsomal catechol-O-methyl-transferase. Life Sci 14: 1089–1100
Broch OJ, jr, Fonnum F (1972) The regional and subcellular distribution of catechol-O-methyl transferase in the rat brain. J Neurochem 19: 2049–2055
Coyle JT, Schwarcz R (1976) Lesion of striatal neurons with kainic acid provides a model for Huntington's chorea. Nature 263: 244–246
Coyle JT, Molliver ME, Kuhar MJ (1978) In situ injections of kainic acid: a new method for selectively lesioning neuronal cell bodies while sparing axons of passage. J Comp Neurol 180: 301–324
Cross AJ, Crow TJ, Killpack WS, Longden A, Owen F, Riley GJ (1978) The activities of brain dopamine-β-hydroxylase and catechol-O-methyl-transferase in schizophrenics and controls. Psychopharmacology 59: 117–121
Garbarg M, Baudry M, Benda P, Schwartz JC (1975) Simultaneous presence of histamine-N-methyltransferase and catechol-O-methyltransferase in neuronal and glial cells in culture. Brain Res 83: 538–541
Inscoe JK, Daly J, Axelrod J (1965) Factors affecting the enzymatic formation of O-methylated dihydroxy derivatives. Biochem Pharmacol 14: 1257–1263
Jeffery DR, Roth JA (1984) Characterization of membrane-bound and solube catechol-O-methyltransferase from human frontal cortex. J Neurochem 42: 826–832
Jonason J, Rutledge CO (1968) The effect of protriptyline on the metabolism of dopamine and noradrenaline in rabbit brainin vitro. Acta Physiol Scand 73: 161–175
Kaplan GP, Hartman BK, Creveling C R (1979) Immunohistochemical demonstration of catechol-O-methyltransferase in mammalian brain. Brain Res 167: 241–250
König JFR, Klippel RA (1963) The rat brain. A stereotaxic atlas of the forebrain and lower parts of the brain stem. Williams and Wilkins, Baltimore
Liesi P, Kaakkola S, Dahl D, Vaheri A (1984) Laminin is induced in astrocytes of adult brain by injury. EMBO J 3: 683–686
Lloyd KG, Davidson L, Hornykiewicz O (1975) The neurochemistry of Parkinson's disease: effect of L-dopa therapy. J Pharmacol Exp Ther 195: 453–464
Marsden CA, Broch OJ, jr, Guldberg HC (1972) Effect of nigral and raphe lesions on the catechol-O-methyltransferase and monoamine oxidase activities in the rat striatum. Eur J Pharmacol 19: 35–42
Nissinen E, Männistö P (1984) Determination of catechol-O-methyltransferase activity by high performance liquid chromatography with electrochemical detection. Anal Biochem 137: 69–73
Rivett AJ, Eddy BJ, Roth JA (1982) Contribution of sulfate conjugation, deamination, and O-methylation to metabolism of dopamine and norepinephrine in human brain. J Neurochem 39: 1009–1016
Rivett AJ, Francis A, Roth JA (1983 a) Localization of membrane-bound catechol-O-methyltransferase. J Neurochem 40: 1494–1496
Rivett AJ, Francis A, Roth JA (1983 b) Distinct cellular localization of membrane-bound and soluble forms of catechol-O-methyltransferase in brain. J Neurochem 40: 215–219
Roth JA (1980) Presence of membrane-bound catechol-O-methyltransferase in human brain. Biochem Pharmacol 29: 3119–3122
Silberstein SD, Shein HM, Berv KR (1972) Catechol-O-methyltransferase and monoamine activity in culture rodent astrocytoma cells. Brain Res 41: 245–248
Skaper SD, Adelson GL, Seegmiller JE (1976) Metabolism of biogenic amines in neuroblastoma and glioma cells in culture. J Neurochem 27: 1065–1070
Ungerstedt U (1971) Postsynaptic supersensitivity after 6-hydroxydopamine-induced degeneration of the nigrostriatal dopamine system. Acta Physiol Scand 82 [Suppl] 367: 69–93
Uretsky NJ, Iversen LL (1970) Effects of 6-hydroxydopamine on catecholamine containing neurones in the rat brain. J Neurochem 17: 269–278
White HL, Wu JC (1975) Properties of catechol-O-methyltransferases from brain and liver of rat and human. Biochem J 145: 135–143
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kaakkola, S., Männistö, P.T. & Nissinen, E. Striatal membrane-bound and soluble catechol-O-methyl-transferase after selective neuronal lesions in the rat. J. Neural Transmission 69, 221–228 (1987). https://doi.org/10.1007/BF01244343
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01244343