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  • Keywords: L-DOPA, Parkinson's disease, dopamine, MPTP, aromatic L-amino acid decarboxylase, nigrostriatal neurons, dopamine D1 receptor antagonists.  (1)
  • Rotational behavior  (1)
  • cholera toxin  (1)
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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 107 (2000), S. 429-443 
    ISSN: 1435-1463
    Keywords: Keywords: L-DOPA, Parkinson's disease, dopamine, MPTP, aromatic L-amino acid decarboxylase, nigrostriatal neurons, dopamine D1 receptor antagonists.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. Exogenous L-DOPA enhances dopamine metabolism in the intact and denervated striatum, and is the treatment of choice for Parkinsonism. Aromatic L-amino acid decarboxylase (AAAD) converts L-DOPA to dopamine. Blockade of dopamine D1-like receptors increases the activity of AAAD in both intact and denervated striatum. A single dose of SCH 23390, a dopamine D1-like receptor antagonist, increases the activity of AAAD in the striatum and midbrain and induces small changes in dopamine metabolism. When L-DOPA is administered after SCH 23390, there is a significant increase in the formation of 3,4-dihydroxyphenylacetic acid and dopamine turnover in striatum and midbrain compared to L-DOPA alone, suggesting further enhancement of dopamine metabolism. When the studies are repeated in the MPTP mouse model of Parkinson's disease, there is significantly more dopamine metabolism in the striatum of lesioned mice pretreated with SCH 23390 than in a comparison group treated with L-DOPA alone. These studies suggest that it may be possible to enhance the conversion of L-DOPA to dopamine in Parkinson's disease patients by administering substances that augment brain AAAD.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1106
    Keywords: Neural transplantation ; Xenograft ; Fetal pig ; Rat striatum ; Rotational behavior ; Tyrosine hydroxylase immunohistochemistry ; Parkinson's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A suspension of cells from embryonic day 21 fetal pig ventral mesencephalon was transplanted into the striatum of 20 immunosuppressed rats with 6-hydroxydopamine-induced lesions of the nigrostriatal dopamine pathway. Of these rats, 15 showed reduction of amphetamine-induced ipsilateral rotation by 9 weeks and complete reversal of rotation by 14–17 weeks. Animals maintained stable reversal of rotations (contralateral direction) until cessation of Cyclosporin A (CyA) treatment at 15–20 weeks. Within 4–9 weeks after CyA removal, these rats showed exclusively ipsilateral rotations during behavioral testing which were comparable to pre-transplant levels, suggesting that the grafts were rejected upon cessation of CyA treatment. Rats were sacrificed and tyrosine hydroxylase (TH) immunohistochemistry was performed at several time points, both on and off CyA, to examine a possible correlation between the degree of rotational behavior and the number of TH- positive surviving grafted cells. Staining showed large numbers (230–12,329) of TH-positive surviving cells in animals displaying a high degree of rotational correction (1.6 to -9.6 net ipsilateral rotations/min) after cessation of CyA treatment. Two control groups, those transplanted with nonneuronal cells from the pig ventral mesencephalon (n=5) and those receiving only daily CyA injections (n=4) showed no significant reduction of net ipsilateral rotations throughout the experiment. No TH-positive surviving cells were seen in the one non-neuronal transplant analyzed. This data demonstrates long-term retention of xenografted tissue with immunosuppression and its concomitant restoration of normal motor behavior in the rat model of Parkinson's disease.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-6830
    Keywords: muscarinic receptors ; adenylate cyclase ; cyclic AMP ; phosphoinositide hydrolysis ; phorbol esters ; pertussis toxin ; cholera toxin ; rat retina
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary 1. Agonist activation of rat retina muscarinic receptors results in suppression of cyclic AMP (cAMP) generation and enhanced phosphoinositide hydrolysis. 2. Pharmacological manipulations that elevate cAMP or stable analogues of cAMP attenuate the acetylcholine (ACh)-induced enhancement of phosphoinositide hydrolysis. We postulate that cross-talk between adenylate cyclase and phospholipase C signal transducing systems probably exists in rat retina, as has been described for other systems. 3. Intraocular administration of pertussis toxin attenuated the response of both adenylate cyclase and phospholipase C to muscarinic stimulation, suggesting that some retinal muscarinic receptors are apparently coupled to their effector systems via pertussis toxin sensitive G proteins.
    Type of Medium: Electronic Resource
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