Thesis (Ph.D) - University of Birmingham, Dept of Medicine, 1993.
|Statement||by Nicholas S.S. Athwal.|
The toxicity of MPTP to dopamine (DA) neurons was studied in dissociated cell cultures from rat embryo mesencephalon. The cultures were exposed to MPTP (from to μM) for 7 days and were analyzed by catecholamine histofluorescence after incubation with α-methylnorepinephrine, by tyrosine hydroxylase (T-OH) immunocytochemistry and by [3 H]DA by: The inhibition of uptake of radioactive dopamine into PC cells by analogues of MPTP with systematic variations of structure was studied in order to assess the steric constraints of the transmembrane dopamine transporter. Of 15 analogues tested, 11 were found to inhibit dopamine uptake, all being competitive by: 2. Di Monte et al. () have recently found that relatively high concentrations of MPTP and MPP' cause cell death in rat hepatocyte suspension through depletion of cell ATP, and that pargyline, an inhibitor of both forms of monoamine oxidase, was capable of preventing MPTP-induced cell death without affecting the toxicity of MPP+.Cited by: The cause of nigral cell death and the underlying mechanism remains elusive. However, the discovery of the selective nigral neurotoxin MPTP and its ability to inhibit mitochondrial energy metabolism via its metabolite MPP+ and to generate superoxide radicals suggests processes by which nigral cell .
MPTP (1-methylphenyl-1,2,3,6-tetrahydropyridine) elicits motor deficits similar to those observed in Parkinson's disease. Before exerting its neurotoxic action, MPTP must be activated by brain monoamine oxidase (MAO) to the neurotoxic metabolite MPP + (1-methylphenylpyridinium). MPTP derivatives differ in their reactivity as MAO substrates and in their neurotoxicity. Dopamine, a principal neurotransmitter, deserves upgrading to ‘NeuroImmunotransmitter’ thanks to its multiple, direct and powerful effects on most/all immune cells. Dopamine by itself is a potent act. We (Nemeroff et al., a, a, ) and others (Goedert, ) have previously reviewed the neuropharmacological, neuroanatomical and neurochemical literature supporting a functional interaction between NT-containing and dopamine-containing cells in the CNS and the interested reader is referred to these articles for a more comprehensive. The review covers the following findings: (i) T cells express functional dopamine receptors (DR s) D1R‐D5R, but their level and function are dynamic and context‐sensitive, (ii) DR membranal protein levels do not necessarily correlate with DR mRNA levels, (iii) different T cell types/subtypes have different DR levels and composition and.
(d) Effect of MPTP and/or deprenyl treatment on the number of TH‐ir cells at 5 dpf. Both concentrations of MPTP decrease the number of TH‐ir cells in populations 3–4, 5,6,11, 7 and Exposure to MPTP μM decreased the number of the cells more than exposure to MPTP μM. J. Med. Chem. All Publications/Website. OR SEARCH CITATIONS. The role of plasma membrane K ATP channels in rotenone-induced cell death remains controversial. Some authors suggest that activation of these channels is neuroprotective during ischemic or toxic. It has subsequently been reported that moderate MPTP exposure in non-human primates damages vesicular monoamine transporter-type 2, which reduces in dopamine storage within the cell, thereby increasing cytosolic dopamine (leading to subsequent ROS generation, again suggesting that this is key pathological event in retrograde degenerations of DA.