Binding and internalization of iodinated neurotensin in neuronal cultures from embryonic mouse brain

Mazella, Jean; Leonard, Kathleen A.; Chabry, Joëlle; Kitabgi, Patrick; Vincent, Jean‐Pierre; Beaudet, Alain

doi:10.1016/0006-8993(91)91460-i

Cited by 53 publications

(27 citation statements)

References 30 publications

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“…In this context, it is interesting to note that, at the level of neurotensinergic pathways, endopeptidase 3.4.24.16-immunopositive astrocytic elements are often directly apposed to endopeptidase 3.4.24.16-immunoreactive nerve cell bodies and/or dendrites (Woulfe et al, 1992). It is therefore tempting to speculate that although the endopeptidase 3.4.24.16 secreted form of astrocytes would act in the extracellular space, thereby restricting diffusion of released neurotensin, the neuronal membraneassociated activity would be responsible for the physiological inactivation of the peptide either in the synaptic cleft, beside neurotensin receptors, or inside early endosomal compartments in which receptor-ligand complexes would have been internalized (Mazella et al, 1991). …”

Section: Discussionmentioning

confidence: 99%

Distinct Properties of Neuronal and Astrocytic Endopeptidase 3.4.24.16: A Study on Differentiation, Subcellular Distribution, and Secretion Processes

et al. 1996

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Endopeptidase 3.4.24.16 belongs to the zinc-containing metalloprotease family and likely participates in the physiological inactivation of neurotensin.The peptidase displays distinct features in pure primary cultured neurons and astrocytes. Neuronal maturation leads to a decrease in the proportion of endopeptidase 3.4.24.16-bearing neurons and to a concomitant increase in endopeptidase 3.4.24.16 activity and mRNA content. By contrast, there is no change with time in endopeptidase 3.4.24.16 activity or content in astrocytes. Primary cultured neurons exhibit both soluble and membrane-associated endopeptidase 3.4.24.16 activity. The latter behaves as an ectopeptidase on intact plated neurons and resists treatments with 0.2% digitonin and Na 2 CO 3 . Further evidence for an association of the enzyme with plasma membranes was provided by cryoprotection experiments and electron microscopic analysis.The membrane-associated form of endopeptidase 3.4.24.16 increased during neuronal differentiation and appears to be mainly responsible for the overall augmentation of endopeptidase 3.4.24.16 activity observed during neuronal maturation. Unlike neurons, astrocytes only contain soluble endopeptidase 3.4.24.16. Astrocytes secrete the enzyme through monensin, brefeldin A, and forskolin-independent mechanisms. This indicates that endopeptidase 3.4.24.16 is not released by classical regulated or constitutive secreting processes. However, secretion is blocked at 4°C and by 8 bromo cAMP and is enhanced at 42°C, two properties reminiscent of that of other secreted proteins lacking a classical signal peptide. By contrast, neurons appear unable to secrete endopeptidase 3.4.24.16.

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Section: Discussionmentioning

confidence: 99%

Distinct Properties of Neuronal and Astrocytic Endopeptidase 3.4.24.16: A Study on Differentiation, Subcellular Distribution, and Secretion Processes

et al. 1996

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“…Conceivably, the receptor is never inserted into these regions. Alternatively, since there is considerable evidence that G-protein-linked peptide receptors are internalized (40,41), these islands may correspond to areas where recently released SP has bound to SPR, migrated to clathrincoated pits, and been endocytosed, leaving a "ghost" of recent synaptic activity behind. This question can be addressed by using in vivo administration of SP in the presence and absence of SP antagonists.…”

Section: Resultsmentioning

confidence: 99%

Synaptic relationship between substance P and the substance P receptor: light and electron microscopic characterization of the mismatch between neuropeptides and their receptors.

Liu

Brown

Jasmin

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

258

153

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At a "classical" neuronal synapse, neurotransmitter is released from presynaptic vesicles by exocytosis, crosses the synaptic cleft, and binds to receptors located postsynaptically. Implicit in this characterization is that neurotransmitter release sites at these synapses are closely apposed to the targeted receptor; neurotransmitter and receptor are separated only by the synaptic cleft and density between pre-and postsynaptic elements (1-4). Examples include glycinergic (3,4) and some glutamatergic synapses (1, 2) in the central nervous system (CNS) and cholinergic synapses in sympathetic ganglia (5) and at the adult neuromuscular junction (6).On the other hand, some -y-aminobutyric acid (GABA) receptors in the cerebellum are located at sites away from GABA-containing synapses, raising the possibility that GABA can act upon targets distant from its site of release, in a "nonsynaptic" fashion. The fact that postsynaptic densities are absent at some CNS monoaminergic synapses (7) suggests that norepinephrine and serotonin have a similar action. Peptide neurotransmitters, which often colocalize with more classical neurotransmitters (8), may also act in a diffuse, nonsynaptic manner. Thus, for example: (i) there are significant mismatches between the distribution of peptides and their respective binding sites (9-11); (ii) peptide neurotransmitters can diffuse away from their site of release (12, 13) and can even be recovered in spinal cord cerebrospinal fluid (14); (iii) binding sites for ju (15) and 8 (16) opioid peptides and for neurotensin (17) rarely overlap synaptic densities; (iv) dense core vesicles that contain neuropeptides are usually located away from the synaptic density, which is the presumed site of release of classical neurotransmitters (18,19); and (v) the locus of exocytosis of dense core vesicles can, in fact, be distant from the synaptic junction (density) (20,21). In the present report we use an antiserum directed against the substance P (SP) receptor (SPR), which corresponds to the NK-1 subtype of tachykinin receptors (22), and demonstrate that there is indeed significant mismatch at the synaptic level between peptide and peptide receptor. Furthermore, we demonstrate that the SPR decorates a large proportion of the somatic and dendritic surface of subpopulations of CNS neurons, indicating that much of the neuronal surface is a potential target of peptide neurotransmitter. METHODSThe studies were performed on male Sprague-Dawley rats (240-260 g) that were deeply anesthetized with sodium pentobarbital (60 mg/kg) and perfused through the ascending aorta with 100 ml of 0.1 M sodium phosphate-buffered saline (PBS; pH 7.4) followed by a 0.1 M sodium phosphatebuffered fixative solution containing either 4.0%o paraformaldehyde (for light microscopy) or 2.0%o glutaraldehyde, 0.5% formaldehyde, and 0.2% picric acid (for both light and electron microscopy), according to the protocol of . After the perfusion the brain and spinal cord were removed and postfixed in the same solution for 2-4 hr.The au...

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“…Warming of fluo-NT-labeled SN17 cells to 37'C both decreased cell surface reactivity and induced internal labeling, suggesting that the tracer had been internalized into the cells. w e r iments carried out with [ 1251]-NT on both SN17 (28) and primary neurons in culture (53) have previously demonstrated the occurrence of receptor-mediated endocytosis of NT in neuronal cells.…”

Section: Discussionmentioning

confidence: 99%

Synthesis of a biologically active fluorescent probe for labeling neurotensin receptors.

Faure¹,

Gaudreau²,

Shaw³

et al. 1994

J Histochem Cytochem.

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Binding and internalization of iodinated neurotensin in neuronal cultures from embryonic mouse brain

Cited by 53 publications

References 30 publications

Distinct Properties of Neuronal and Astrocytic Endopeptidase 3.4.24.16: A Study on Differentiation, Subcellular Distribution, and Secretion Processes

Distinct Properties of Neuronal and Astrocytic Endopeptidase 3.4.24.16: A Study on Differentiation, Subcellular Distribution, and Secretion Processes

Synaptic relationship between substance P and the substance P receptor: light and electron microscopic characterization of the mismatch between neuropeptides and their receptors.

Synthesis of a biologically active fluorescent probe for labeling neurotensin receptors.

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