Receptor Endocytosis and Dendrite Reshaping in Spinal Neurons After Somatosensory Stimulation

Mantyh, Patrick W.; DeMaster, Eric; Malhotra, Amit D.; Ghilardi, Joseph R.; Rogers, Scott D.; Mantyh, Christopher R.; Liu, Hantao; Basbaum, Allan I.; Vigna, Steven R.; Maggio, John E.; Simone, Donald A.

doi:10.1126/science.7539937

Cited by 463 publications

(281 citation statements)

References 34 publications

(11 reference statements)

Supporting

Mentioning

258

Contrasting

Unclassified

Order By: Relevance

“…There has been considerable recent interest in endocytosis of the NK1-R for the peptide SP, which has been studied in transfected epithelial cells, in primary cultures of enteric neurons and in endothelial cells of post-capillary venules and neurons of the central nervous system in the intact animal [142,[146][147][148][149][150][151] (Figures 6a and 7a). SP and its receptor are internalized into early endosomes by a clathrin-mediated mechanism, and subsequent endosomal acidification permits dissociation of the ligand and its receptor and sorting into different pathways : SP is degraded in lysosomes and the NK1-R appears to be recycled.…”

Section: Pathways Of Agonist-induced Receptor Endocytosis and Trafficmentioning

confidence: 99%

Regulatory mechanisms that modulate signalling by G-protein-coupled receptors

Böhm

Grady

Bunnett

1997

Biochemical Journal

476

322

View full text Add to dashboard Cite

The large and functionally diverse group of G-protein-coupled receptors includes receptors for many different signalling molecules, including peptide and non-peptide hormones and neurotransmitters, chemokines, prostanoids and proteinases. Their principal function is to transmit information about the extracellular environment to the interior of the cell by interacting with the heterotrimeric G-proteins, and they thereby participate in many aspects of regulation. Cellular responses to agonists of these receptors are usually rapidly attenuated. Mechanisms of signal attenuation include removal of agonists from the extracellular fluid, receptor desensitization, endocytosis and downregulation. Agonists are removed by dilution, uptake by transporters and enzymic degradation. Receptor desensitization is mediated by receptor phosphorylation by G-protein receptor kinases and second-messenger kinases, interaction of phosphorylated receptors with arrestins and receptor uncoupling from

show abstract

Section: Pathways Of Agonist-induced Receptor Endocytosis and Trafficmentioning

confidence: 99%

Regulatory mechanisms that modulate signalling by G-protein-coupled receptors

Böhm

Grady

Bunnett

1997

Biochemical Journal

476

322

View full text Add to dashboard Cite

show abstract

“…The amount of NK1R internalization was quantified using a standard method (Mantyh et al, 1995;Abbadie et al, 1997;Honore et al, 1999;Schwei et al, 1999;Trafton et al, 1999; with minor modifications (Marvizon et al, 1997;1999a). Briefly, we determined the percentage of NK1R immunoreactive neurons in lamina I that show internalization in relation to the total number of NK1R neurons sampled.…”

Section: Quantification Of Nk1r Internalizationmentioning

confidence: 99%

“…In contrast, we show here that inhibitors of NEN and DEC produced a relatively smaller increase (2.8 -3.5 times) in the potencies of SP and NKA to produce NK1R internalization. Moreover, whereas peptidase inhibitors are required to observe m-opioid receptor internalization in dorsal horn neurons produced by endogenously released opioids (Song & Marvizon, 2003), endogenously released neurokinins produce abundant NK1R internalization in the absence of peptidase inhibitors (Mantyh et al, 1995;Allen et al, 1997;Liu et al, 1997;Marvizon et al, 1997;1999a;Cao et al, 1998;Honore et al, 1999;Riley et al, 2001). Therefore, it is possible to use peptidase inhibitors to enhance the analgesic effect of endogenous opioids (Noble et al, 1992b;Roques, 2000) without increasing NK1R activation by endogenous neurokinins.…”

Section: Jcg Marvizón Et Al Effect Of Peptidases On Nk1r Internalimentioning

confidence: 99%

“…NK1R activation was measured by their internalization, a technique validated in numerous studies (Mantyh et al, 1995;Allen et al, 1997;Liu et al, 1997;Marvizon et al, 1997;1999a;Cao et al, 1998;Honore et al, 1999;Riley et al, 2001). An additional goal of this study was to compare the potencies of SP, NKA and NKB to produce NK1R internalization.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effect of peptidases on the ability of exogenous and endogenous neurokinins to produce neurokinin 1 receptor internalization in the rat spinal cord

Marvizón¹,

Wang

Lao³

et al. 2003

British J Pharmacology

View full text Add to dashboard Cite

1 The ability of peptidases to restrict neurokinin 1 receptor (NK1R) activation by exogenously applied or endogenously released neurokinins was investigated by measuring NK1R internalization in rat spinal cord slices. 2 Concentration -response curves for substance P and neurokinin A were obtained in the presence and absence of 10 mM thiorphan, an inhibitor of neutral endopeptidase (EC 3.4.24.11), plus 10 mM captopril, an inhibitor of dipeptidyl carboxypeptidase (EC 3.4.15.1). These inhibitors significantly decreased the EC 50 of substance P to produce NK1R internalization from 32 to 9 nM, and the EC 50 of neurokinin A from 170 to 60 nM. 3 Substance P was significantly more potent than neurokinin A, both with and without these peptidase inhibitors. 4 In the presence of peptidase inhibitors, neurokinin B was 10 times less potent than neurokinin A and 64 times less potent than substance P (EC 50 ¼ 573 nM). 5 Several aminopeptidase inhibitors (actinonin, amastatin, bacitracin, bestatin and puromycin) failed to further increase the effect of thiorphan plus captopril on the NK1R internalization produced by 10 nM substance P. 6 Electrical stimulation of the dorsal root produced NK1R internalization by releasing endogenous neurokinins. Thiorphan plus captopril increased NK1R internalization produced by 1 Hz stimulation, but not by 30 Hz stimulation. 7 Therefore, NEN and DCP restrict NK1R activation by endogenous neurokinins when they are gradually released by low-frequency firing of primary afferents, but become saturated or inhibited when primary afferents fire at a high frequency.

show abstract

“…This approach provides an ideal way to locate the areas of opioid release, because MORs serve as opioid detectors located in close proximity to opioid-releasing terminals and able to detect all naturally-occurring MOR agonists (Song and Marvizon, 2003a). Previously, neurokinin 1 receptor (NK1R) internalization had been used to measure substance P release (Abbadie et al, 1997;Allen et al, 1997;Honore et al, 1999;Kondo et al, 2005;Mantyh et al, 1995;Marvizon et al, 1997;Marvizon et al, 2003). Importantly, the magnitude of NK1R internalization increased with the intensity of the stimulus used to evoke substance P release, both when a noxious stimulus was used in vivo (Allen et al, 1997), or a chemical stimulus in vitro .…”

Section: Introductionmentioning

confidence: 99%

Noxious mechanical stimulation evokes the segmental release of opioid peptides that induce μ-opioid receptor internalization in the presence of peptidase inhibitors

et al. 2008

View full text Add to dashboard Cite

The internalization of μ-opioid receptors (MORs) provides an ideal way to locate areas of opioid peptide release. We used this method to study opioid release in the spinal cord evoked by noxious stimuli in anesthetized rats. Previous studies have shown that opioids released in the spinal cord produce MOR internalization only when they are protected from peptidase degradation. Accordingly, rats were implanted with chronic intrathecal catheters that were used to inject a mixture of peptidase inhibitors (amastatin, captopril and phosphoramidon) onto the lumbar spinal cord. Five minutes later, a noxious stimulus was delivered to the paw. Lumbar spinal segments were double-stained with antibodies against MORs and neurokinin 1 receptors (NK1Rs) using immunofluorescence. Mechanical stimulation of the hindpaw consisted of repeated 10 sec clamps with a hemostat for 10 min. In the ipsilateral dorsal horn, the stimulus produced abundant NK1R internalization in segments L3-L6, and a more modest but significant MOR internalization in segments L5 and L6. In the contralateral dorsal horn, NK1R was substantially lower and MOR internalization was negligible. The same mechanical stimulus applied to a forepaw did not produce NK1R or MOR internalization in the lumbar spinal cord. Thermal stimulation consisted of immersing a hindpaw in water at 52 °C for 2 min. It produced substantial NK1R internalization ipsilaterally in segment L6, but no MOR internalization. These results show that mechanical stimulation induces segmental opioid release, i.e., in the dorsal horn receiving the noxious signals and not in other spinal segments.

show abstract

Receptor Endocytosis and Dendrite Reshaping in Spinal Neurons After Somatosensory Stimulation

Cited by 463 publications

References 34 publications

Regulatory mechanisms that modulate signalling by G-protein-coupled receptors

Regulatory mechanisms that modulate signalling by G-protein-coupled receptors

Effect of peptidases on the ability of exogenous and endogenous neurokinins to produce neurokinin 1 receptor internalization in the rat spinal cord

Noxious mechanical stimulation evokes the segmental release of opioid peptides that induce μ-opioid receptor internalization in the presence of peptidase inhibitors

Contact Info

Product

Resources

About