Topic
Polyamine binding
About: Polyamine binding is a research topic. Over the lifetime, 188 publications have been published within this topic receiving 9206 citations.
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TL;DR: Selegiline appears to exhibit other mechanisms of action which are independent of its action on MAO-B, including induction of superoxide dismutase, stimulation of neurotrophic factor synthesis, antagonistic modulation of the polyamine binding site of the NMDA-receptor
Abstract: Recent findings emphasize the significance of oxidative mechanisms, involving the activity of monoamine oxidase (MAO) and the formation of free radicals, in the pathogenesis of Parkinson’s disease. The possible role of such mechanisms in the degeneration of neurones in the substantia nigra has led to clinical trials aimed at preventing or slowing the progressively disabling course of the disease. However, conclusive clinical evidence of a neuroprotective effect in PD is still lacking. In this paper, we discuss possible mechanisms by which selegiline manifests neuroprotective effects in experimental and clinical situations. Besides MAO-B inhibition, which above all explains the prevention of protoxin activation and substrate oxidation by MAO-B, selegiline appears to exhibit other mechanisms of action (induction of Superoxide dismutase, stimulation of neurotrophic factor synthesis, antagonistic modulation of the polyamine binding site of the NMDA-receptor) which are independent of its action on MAO-B.
18 citations
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TL;DR: The studies have shown, for the first time, the presence of specific [3H]-ifenprodil binding sites in the human retina with pharmacological characteristics of PBS associated with the NMDA receptor ionophore complex.
Abstract: AIMS—This study characterised the pharmacology of [3H]-ifenprodil binding to the polyamine binding sites (PBS) on the N-methyl-D-aspartate (NMDA) receptor channel complex on human retinas These data were correlated with the known neuroprotective effects of ifenprodil and eliprodil
METHODS—Specific binding of [3H]-ifenprodil (under sigma site blockade) was investigated using human retinal homogenates and radioligand binding techniques Scatchard and competition analyses were utilised to define the pharmacology of the [3H]-ifenprodil binding sites
RESULTS—Specific binding of [3H]-ifenprodil comprised 73% (SEM 3%) of total and reflected interaction with two affinity sites (Kds = 039 and 43 µM) of different densities (Bmax = 144 and 105 pmol/ mg protein) (n = 5) The rank order of affinity of compounds competing for [3H]-ifenprodil binding to the high affinity PBS was: ifenprodil > eliprodil > arcaine > spermine > diaminodecane > spermidine > putrescine >> MK-801 (n = 3-7) However, [3H]-ifenprodil binding was minimally inhibited by glutamate, NMDA, and kainate
CONCLUSION—These studies have shown, for the first time, the presence of specific [3H]-ifenprodil binding sites in the human retina with pharmacological characteristics of PBS associated with the NMDA receptor ionophore complex The neuroprotective effects of eliprodil and ifenprodil may, in part, be mediated via these [3H]-ifenprodil labelled sites
Keywords: retina; neuroprotection; eliprodil; NMDA receptors
18 citations
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TL;DR: Results suggest that state dependency induced by arcaine involves the opioid system, and that arcaine-induced impairment of IA performance was completely transferred to morphine and vice versa.
Abstract: Rationale
Arcaine is a competitive antagonist of the polyamine binding site at the N-methyl-D-aspartic acid receptor which induces state-dependent recall. However, no study has addressed the involvement of other neurotransmitter/neuromodulators in arcaine-induced state dependency.
18 citations
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TL;DR: The structure of this PA(222) molecule presents the previously reported zig‐zag type conformation, and comparison of this structure with other polyamine–DNA cocrystals reveals structural themes and differences that may relate to the length of the polyamine.
17 citations
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TL;DR: Polyamines and the n-methyl-d-aspartate receptor modulate excitotoxic responses to cryo-injury in pericapillary cerebral astrocytes.
Abstract: Four hours following cryo-injury rat cerebral pericapillary astrocytes from the perilesional area were markedly swollen occupying 17% of the pericapillary space as compared to 11% in sham operated controls. Ornithine decarboxylase activity and polyamine levels were increased over sham controls. The astrocytic swelling, the percentage of the pericapillary space occupied by astrocytic processes, and polyamine levels were reduced to near control levels by the following: (1) α-difluoromethylornithine; (2) Ifenprodil; and (3) MK-801. α-Difluoromethylornithine is a specific inhibitor of ornithine decarboxylase, Ifenprodil is an inhibitor of the polyamine binding site on the n-methyl-d-aspartate receptor, and MK-801 is an antagonist to n-methyl-d-aspartate binding to the n-methyl-d-aspartate receptor. Addition of putrescine, the product of ornithine decarboxylase activity, reversed the effect of α-difluoromethylornithine and restored the pericapillary swelling. Putrescine did not affect the MK-801-induced reduction in pericapillary astrocytic swelling. Therefore, polyamines and the n-methyl-d-aspartate receptor modulate excitotoxic responses to cryo-injury in pericapillary cerebral astrocytes.
17 citations