Effects of inhibition of membrane-bound metalloendopeptidase (EC 3.4.24.11) on the firing of neurones in the substantia nigra of the rat.
Item
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Title
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Effects of inhibition of membrane-bound metalloendopeptidase (EC 3.4.24.11) on the firing of neurones in the substantia nigra of the rat.
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Identifier
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AAI9000016
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identifier
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9000016
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Creator
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Bier, Michael Jeffrey.
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Contributor
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Adviser: Sherwin Wilk
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Date
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1989
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Neuroscience
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Abstract
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The effect of inhibitors of the membrane-bound metalloendopeptidase-24.11 ('enkephalinase') on the activity of electrophysiologically identifiable dopaminergic and non-dopaminergic neurones in the substantial nigra of the rat is described. Infusion of 1 umol of N- (1-(R,S)-carboxy- 2-phenylethyl) Phe-pAB (CPAB), 1 or 2 umol of N- (1-(R,S)- carboxy-3-phenylpropyl) Phe-pAB (CPPAB) into the lateral ventricle produced significant increases in the spontaneous activity and short latency evoked responses of non-dopaminergic and dopaminergic cells.;Inhibitors were administered directly into the nigra and striatum in order to localize the possible site of action of the CPAB i.c.v. effects. Perfusion of approximately 4% of the striatum with 1 uL of a 40 millimolar solution of CPAB produces 60% of the response on spontaneous activity of non-dopaminergic and 30% of the response of dopaminergic cells obtained following i.c.v. administration of CPAB. Treatment of approximately 4% of the striatum with CPAB produces 25% of the evoked response of dopaminergic cells obtained following CPAB i.c.v.;Application of 0.04 umol CPAB (a dose which was determined to yield inhibition of enzyme activity nearly equivalent to CPAB i.c.v.) into the substantia nigra had no significant effect on the spontaneous activity of nigral neurons. Significant increases in the magnitude of the evoked response of non-dopaminergic (average increase 35%) but not dopaminergic cells was observed following inhibition of the activity of 24.11 in the substantia nigra.;Application of 1 mg/kg, i.v. naloxone is able to antagonize the effect of CPAB i.c.v. on the magnitude of the evoked response of non-dopaminergic cells. Application of 1 mg/kg, i.v. naloxone is able to reverse the effect of CPAB i.c.v. on the magnitude of the evoked response of dopaminergic cells. Enhanced opioid peptide activity in the striatum and nigra are necessary for full expression of the CPAB i.c.v. effect. (Abstract shortened with permission of author.).
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
