Effect of peptidase inhibition on the pattern of intraspinally released immunoreactive substance P detected with antibody microprobes

Duggan, A.W.; Schaible, Hans‐Georg; Hope, P.J.; Lang, C.W.

doi:10.1016/0006-8993(92)90059-i

Cited by 54 publications

(23 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, none of the aminopeptidase inhibitors that we tested, including bacitracin, increased NK1R internalization produced by a low concentration of SP. It is difficult to reconcile our results using bacitracin with those of Mauborgne et al (1991), particularly in view of the fact that they found no effect for NEN and DCP inhibitors, in contrast with our findings and those of other investigators (Geppetti et al 1989;Duggan et al, 1992). We cannot rule out that neurokinins are degraded by aminopeptidases that are not inhibited by the compounds that we used.…”

Section: Jcg Marvizón Et Alcontrasting

confidence: 99%

“…Geppetti et al (1989) found that captopril did not affect capsaicin-evoked SP release from guinea-pig dorsal horn slices, whereas thiorphan produced a 2.4-fold increase in SP release. Similarly, Duggan et al (1992) found that the addition of the DCP inhibitor enalaprilat did not increase SP release from the cat spinal cord observed in the presence of the NEN inhibitor kelatorphan. Therefore, NEN appears to be the main enzyme degrading SP.…”

Section: Jcg Marvizón Et Almentioning

confidence: 78%

“…The peptidase inhibitors used were thiorphan, an NEN inhibitor, and captopril, a DCP inhibitor. Inhibitors of NEN and DCP have been found to increase the release of SP (Duggan et al, 1992), and are routinely used to protect released SP against degradation (Malcangio & Bowery, 1993;Malcangio et al, 1997;Lever & Malcangio, 2002). Thiorphan and captopril were both used at 10 mM, a concentration at which they completely protect opioid peptides against degradation (Suzuki et al, 1997;Hiranuma et al, 1998;Song & Marvizon, 2003) and increase responses to SP and NKA in the spinal cord (Suzuki et al, 1994).…”

Section: Resultsmentioning

confidence: 99%

“…For example, Geppetti et al (1989) found that thiorphan increased SP release from the guinea-pig spinal cord 2.4 times. Duggan et al (1992) reported that spinal injections of the NEN inhibitor kelatorphan combined with the DCP inhibitor enalaprilat increased the amount of SP release evoked by primary afferent stimulation. However, relating SP release with NK1R activation is not straightforward: when Figure 4 Lack of the effect of aminopeptidase inhibitors on SPinduced NK1R internalization.…”

Section: Discussionmentioning

confidence: 99%

“…In particular, neutral endopeptidase (NEN,EC 3.4.24.11) and dipeptidyl carboxypeptidase (DCP,EC 3.4.15.1) appear to degrade neurokinins in the dorsal horn, because inhibitors of these enzymes increased the amount of released SP detected using antibody microprobes (Duggan et al, 1992). Other studies indicated that aminopeptidases (EC 3.4.11.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

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

Section: Jcg Marvizón Et Alcontrasting

confidence: 99%

Section: Jcg Marvizón Et Almentioning

confidence: 78%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

show abstract

Immunocytochemical localization of substance P receptor in rat periaqueductal gray matter: A light and electron microscopic study

Barbaresi

1998

J. Comp. Neurol.

View full text Add to dashboard Cite

The distribution of substance P receptor (SPR) protein in the rat periaqueductal gray matter (PAG) was investigated with a polyclonal antibody in the four subdivisions obtained by cytochrome-oxidase histochemistry (Co-hi). At light microscopic analysis, immunoreactivity appeared particularly dense in the dorsal subdivision of the PAG, was less intense in the other subdivisions, and formed several longitudinally organized columns. SPR-like immunoreactivity (SP(R-i)) was localized mostly to cell bodies and dendrites of small and medium-sized neurons, which constituted about 6% of the total neuronal population of the PAG. At the electron microscopic level, SP(R-i) could be observed on postsynaptic as well as on nonsynaptic regions of both cell bodies and dendrites. A small proportion of axons (4.2%) and axon terminals (5.3%) showed SP(R-i), the majority of labeled axon terminals, amounting to about 70% of synapsing elements, formed asymmetric synapses with dendrites. Rare astroglial processes displaying SP(R-i) were also observed scattered throughout the neuropil of all PAG subdivisions. Our observations suggest that 1) also in the PAG, SP may act in a diffuse, nonsynaptic manner, probably on targets that are distant from its sites of release; and 2) SP may modulate excitatory neurotransmission acting presynaptically on those labeled axons that form asymmetric synapses.

show abstract

Cellular and subcellular distribution of substance P receptor immunoreactivity in the dorsal vagal complex of the rat and cat: A light and electron microscope study

Baude

Shigemoto

1998

J. Comp. Neurol.

View full text Add to dashboard Cite

Immunoreactivity for the substance P receptor (NK1 receptor) has been investigated by light and electron microscopy in the dorsal vagal complexes of adult rats and cats. The general pattern of NK1 immunoreactivity was similar for both rat and cat. Numerous NK1-immunoreactive neurons were present in the area postrema, the nucleus of the solitary tract, and the dorsal motor nucleus of the vagus nerve. The density of labelled neurons differed between the subnuclei of the nucleus of the solitary tract. Overall, the efferent neurons of the dorsal motor nucleus of the vagus nerve highly expressed NK1 when compared to neurons in the nucleus of the solitary tract. The results are discussed with reference to the viscerotopic organisation of the dorsal vagal complex. Ultrastructural analysis demonstrated that NK1 immunoreactivity was present only at the membrane surface of somatic and dendritic profiles of neurons. No labelling was found in axon terminals, axons, or glial processes. NK1 immunoreactivity, as revealed by a preembedding immunogold technique in serial ultrathin sections, was preferentially located at nonsynaptic sites. A semiquantitative study suggested that the density of NK1 receptors is statistically higher at membrane sites free of any contact (synaptic or not) with axon terminals. The subcellular localisation of NK1 immunoreactivity was similar for neurons of both rat and cat. These results suggest that in the dorsal vagal complex, substance P might act on NK1 receptors through a process of volume transmission.

show abstract

Effect of peptidase inhibition on the pattern of intraspinally released immunoreactive substance P detected with antibody microprobes

Cited by 54 publications

References 26 publications

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

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

Immunocytochemical localization of substance P receptor in rat periaqueductal gray matter: A light and electron microscopic study

Cellular and subcellular distribution of substance P receptor immunoreactivity in the dorsal vagal complex of the rat and cat: A light and electron microscope study

Contact Info

Product

Resources

About