Differential effects of wortmannin on the release of substance P and amino acids from the isolated spinal cord of the neonatal rat

Suzuki, Hidenori; Yoshioka, Koichi; Maehara, Taketoshi; Guo, Jian-Zhong; Nonomura, Yoshiaki; Otsuka, Masanori

doi:10.1038/sj.bjp.0702243

Cited by 7 publications

(5 citation statements)

References 29 publications

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“…Previous studies have demonstrated the importance of various intracellular signaling factors, including MAP kinases, in the regulation of SP release from neurons (Suzuki et al. 1998; Tang et al.…”

Section: Resultsmentioning

confidence: 99%

Activation of transient receptor potential ankyrin 1 evokes nociception through substance P release from primary sensory neurons

Nakamura

Une

Miyano³

et al. 2012

Journal of Neurochemistry

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To examine mechanisms underlying substance P (SP) release from primary sensory neurons in response to activation of the non-selective cation channel transient receptor potential ankyrin 1 (TRPA1), SP release from cultured rat dorsal root ganglion neurons was measured, using radioimmunoassay, by stimulating TRPA1 with allyl isothiocyanate (AITC), a TRPA1 agonist. AITC-evoked SP release occurred in a concentration-and time-dependent manner. Interestingly, p38 mitogen-activated protein kinase (p38) inhibitor SB203580 significantly attenuated AITC-evoked SP release. The in vivo effect of AITC-evoked SP release from primary sensory neurons in mice was evaluated. Hind paw intraplantar injection of AITC induced nociceptive behaviors and inflammation (edema, thermal hyperalgesia). AITC-induced thermal hyperalgesia and edema were inhibited by intraplantar pre-treatment with either SB203580 or neurokinin-1 receptor antagonist CP96345. Moreover, intrathecal pre-treatment with either CP96345 or SB203580 inhibited AITC-induced nociceptive behaviors and thermal hyperalgesia. Immunohistochemical studies demonstrated that intraplantar AITC injection induced the phosphorylation of p38 in mouse dorsal root ganglion neurons containing SP. These findings suggest that activation of TRPA1 evokes SP release from the primary sensory neurons through phosphorylation of p38, subsequent nociceptive behaviors and inflammatory responses. Furthermore, the data also indicate that blocking the effects of TRPA1 activation at the periphery leads to significant antinociception.

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Section: Resultsmentioning

confidence: 99%

Activation of transient receptor potential ankyrin 1 evokes nociception through substance P release from primary sensory neurons

Nakamura

Une

Miyano³

et al. 2012

Journal of Neurochemistry

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“…Notwithstanding their identity, binding of the transmitter-containing SVs and/or LDCVs to PtdIns(4,5)P 2 would target the release of their transmitters to specific microdomains in the plasma membrane. A role of other phosphorylated phosphoinositide recruitment sites in differential regulation of LDCV and SV exocytosis was proposed by experiments in rat spinal cord [120]. Pharmacological blockade of phosphatidylinositol 3-kinase selectively reduced release of substance-P peptide without affecting the release of glutamate and GABA.…”

Section: Inositol Phosphate Signaling and Differential Neurotransmittmentioning

confidence: 98%

Differential signaling in presynaptic neurotransmitter release

Ghijsen

Leenders

2005

CMLS, Cell. Mol. Life Sci.

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Neuronal communication is tightly regulated by presynaptic signaling, thereby temporarily and locally secreting one or more transmitters in order to exert propagation or modulation of network activity. In the last 2 decades our insight into the molecular regulation of presynaptic transmitter vesicle traffic and fusion has exponentionally grown due to the identification of specific functional interactions between presynaptic proteins involved in these processes. In addition, a plethora of extracellular and intracellular messengers regulate neurotransmitter release, occasionally leading to short- or long-term adaptations of the synapse to altered environmental signals. Important in this respect is the ability of various nerve terminals to diverge their output by differentiation in secretion of co-localized transmitters. This divergence in presynaptic signaling may converge in the postsynaptic target neuron or spread to neighbouring cells. In this review differential presynaptic signaling mechanisms will be related to their potential divergent roles in transmitter release.

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“…A precise role for PI 3-kinase in nerve terminal function has not been established (12)(13)(14), despite that its lipid products play numerous roles the actin cytoskeleton and in vesicle trafficking (15, 16). Synapsin I also connects vesicle traffic with the actin cytoskeleton and the synapsin-p85 in vitro interaction suggests that PI 3-kinase activity might play a role in SV recycling if it occurred in nerve terminals.…”

mentioning

confidence: 99%

Synapsin I-associated Phosphatidylinositol 3-Kinase Mediates Synaptic Vesicle Delivery to the Readily Releasable Pool

Cousin

Malladi

Tan

et al. 2003

Journal of Biological Chemistry

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Maintaining synaptic transmission requires replenishment of docked synaptic vesicles within the readily releasable pool (RRP) from synaptic vesicle clusters in the synapsin-bound reserve pool. We show that synapsin forms a complex with phosphatidylinositol 3-kinase (PI 3-kinase) in intact nerve terminals and that synapsinassociated kinase activity increases on depolarization. Disruption of either PI 3-kinase activity or its interaction with synapsin inhibited replenishment of the RRP, but did not affect exocytosis from the RRP. Thus we conclude that a synapsin-associated PI 3-kinase activity plays a role in synaptic vesicle delivery to the RRP. This also suggests that PI 3-kinase contributes to the maintenance of synaptic transmission during periods of high activity, indicating a possible role in synaptic plasticity.A typical nerve terminal in the central nervous system contains about 200 -250 synaptic vesicles (SVs).1 These can be functionally divided into a small readily releasable pool (RRP) and a large reserve pool. The RRP contains less than 5% of total nerve terminal SVs and is defined morphologically as predocked SVs at the active zone and functionally as SVs that are primed and immediately available for the initial rapid phase of neurotransmitter release (1). The remainder constitutes the reserve pool, which ensures that a continual supply of SVs is available for delivery to the RRP and is drawn upon to maintain neurotransmission during periods of intense or prolonged stimulation (2-4). The reserve pool SVs surround the active zone and are clustered together in an actin-based cytoskeletal matrix via an interaction with synapsins (3, 5).There are five synapsin proteins (Ia, Ib, IIa, IIb, and III) from three genes (I, II, and III) (6), which maintain the reserve pool SVs as a cluster and prevent their free dispersal within the terminal. Synapsins I and II control SV replenishment of the RRP, because conditions that disrupt their function result in dispersal or depletion of SV clusters near the active zone and enhance synaptic depression (3, 5, 7). In contrast, disruption of the much less abundant synapsin III does not affect SV clusters and reduces synaptic depression (8). SV liberation from clusters within the actin cytomatrix is mediated by the multi-site phosphorylation of synapsin I and II, which decreases their affinity for SVs or actin (6). Disruption of synapsin I phosphorylation sites thus reduces the number of SVs undergoing exocytosis (9). It is unknown how liberated SVs translocate to the RRP, and the mechanisms governing entry into the RRP (docking/priming) are incompletely understood (10).Synapsin I has a C-terminal proline-rich domain that interacts with src homology 3 (SH3) domains present in a large number of proteins, including the p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase) (6, 11). A precise role for PI 3-kinase in nerve terminal function has not been established (12)(13)(14), despite that its lipid products play numerous roles the actin cytoskeleton and in vesicle traffic...

show abstract

Differential effects of wortmannin on the release of substance P and amino acids from the isolated spinal cord of the neonatal rat

Cited by 7 publications

References 29 publications

Activation of transient receptor potential ankyrin 1 evokes nociception through substance P release from primary sensory neurons

Activation of transient receptor potential ankyrin 1 evokes nociception through substance P release from primary sensory neurons

Differential signaling in presynaptic neurotransmitter release

Synapsin I-associated Phosphatidylinositol 3-Kinase Mediates Synaptic Vesicle Delivery to the Readily Releasable Pool

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