Neurokinin B is a preferred agonist for a neuronal substance P receptor and its action is antagonized by enkephalin.

Laufer, Ralph; Wormser, Uri; Friedman, Zeev; Gilon, Chaim; Chorev, Michael; Selinger, Zvi

doi:10.1073/pnas.82.21.7444

Cited by 155 publications

(77 citation statements)

References 24 publications

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“…NK-3 receptors also mediate increased phosphoinositide hydrolysis in guinea pig ileum and neonatal rat spinal cord [2,8]. In addition, NK-3 receptors depolarize guinea pig myenteric neurons to augment release of acetyleholine [9][10][11], stimulate contraction of the rat portal vein [12] and modulate both serotinergieand ¢holinergic-dependent behavioural responses in mouse and rat [13,14]. Despite these observations indicating an important physiological role controlling transmitter release and vascular tone in some species, NK-3 receptors have not been identified in human tisCorrespondeneeaddreas: ( sues.…”

Section: Introductionmentioning

confidence: 99%

Molecular characterisation, expression and localisation of human neurokinin‐3 receptor

Buell¹,

Schulz²,

Arkinstall³

et al. 1992

FEBS Letters

101

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The complete amino acid sequence of the human neurokinin-3 receptor was deduced by DNA sgqumtco analysis of human genomic fragments. Comparison of the predicted primary structure with those for the human neurokinin receptors 1 and 2 shows a highly conserved pattern of seven hydrophobi¢ regions with maximum divergence oceuring at the amino-and carboxy-terrnini, The position of intron-exon junctions are identical to those in other reported neurokinin genes, Using a chimeric genomic.cDNA gone, the human NK-3 receptor was expressed in Xenopus laevts oooytes where it mediates membrane conductance changes in response to its agonist, neurokinin B. More significantly, expression of the 8ene in mammalian cells resulted in detection of receptor binding as well as neurokinin-stimulated calcium mobilization and araehidonie acid release, all displaying the pharmacological characteristics expected of a nearokinin-3 receptor, By using the polymerase chain reaction we have shown that mRNA for the human neurokinin-3 receptor is expressed predominantly in the egntral nervous system,

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Section: Introductionmentioning

confidence: 99%

Molecular characterisation, expression and localisation of human neurokinin‐3 receptor

Buell¹,

Schulz²,

Arkinstall³

et al. 1992

FEBS Letters

101

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“…8A). Equal concentrations of SP and BK were used, because the potency of BK at B 2 receptors and SP at NK1 receptors are comparable in neurons and both have an EC 50 in the low nanomolar range (12,40). Remarkably, in the nocifensive behavior test (total time of paw biting, licking, and flinching) BK, but not SP, produced prominent spontaneous pain (Fig.…”

Section: Sp Augments M Current In Sensory Neurons Via Oxidativementioning

confidence: 99%

Reactive oxygen species are second messengers of neurokinin signaling in peripheral sensory neurons

Linley¹,

Ooi

Pettinger³

et al. 2012

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

108

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Substance P (SP) is a prominent neuromodulator, which is produced and released by peripheral damage-sensing (nociceptive) neurons; these neurons also express SP receptors. However, the mechanisms of peripheral SP signaling are poorly understood. We report a signaling pathway of SP in nociceptive neurons: Acting predominantly through NK1 receptors and G i/o proteins, SP stimulates increased release of reactive oxygen species from the mitochondrial electron transport chain. Reactive oxygen species, functioning as second messengers, induce oxidative modification and augment M-type potassium channels, thereby suppressing excitability. This signaling cascade requires activation of phospholipase C but is largely uncoupled from the inositol 1,4,5-trisphosphate sensitive Ca 2+ stores. In rats SP causes sensitization of TRPV1 and produces thermal hyperalgesia. However, the lack of coupling between SP signaling and inositol 1,4,5-trisphosphate sensitive Ca 2+ stores, together with the augmenting effect on M channels, renders the SP pathway ineffective to excite nociceptors acutely and produce spontaneous pain. Our study describes a mechanism for neurokinin signaling in sensory neurons and provides evidence that spontaneous pain and hyperalgesia can have distinct underlying mechanisms within a single nociceptive neuron.G protein coupled receptors | inflammatory pain | intracellular signaling | KCNQ | M current E xcitation of peripheral terminals of sensory neurons is a primary event in somatosensation, including pain. A large proportion of sensory neurons (mostly TRPV1 + damage-sensing or "nociceptive" neurons) produce neuropeptides such as substance P (SP), which are released in response to nociceptive stimulation both at spinal cord synapses and in the periphery (1). In the spinal cord SP acts as an excitatory neurotransmitter or cotransmitter (2, 3), whereas peripheral SP release is thought to underlie the inflammatory response known as "neurogenic inflammation" (4). Many peripheral nociceptors also express receptors for SP [neurokinin receptors (NKR) 1-3 (NK1-3)]; this expression may suggest paracrine or autocrine actions of this peptide. However, the nature of such actions is controversial, and the molecular events triggered by NKR in peripheral nociceptors are not well established. The NKR traditionally are classed as G q/11 -coupled G protein-coupled receptors (GPCR) that activate phospholipase C (PLC), with subsequent hydrolysis of membrane phosphatidylinositol 4,5-bisphosphate (PIP 2 ) and release of inositol 1,4,5-trisphosphate (IP 3 ) and diacylglycerol (DAG) (5, 6). Common downstream steps of G q/11 signaling include IP 3 -mediated release of Ca 2+ from intracellular stores and DAG-mediated activation of PKC. However, it was hitherto unknown whether NKR in peripheral sensory neurons couple fully to this signaling cascade, because a lack of coupling between NKR and Ca 2+ release in dorsal root ganglia (DRG) neurons has been noted (ref. 7 and 8, but cf. ref. 9). Nevertheless, it is accepted that peripherally act...

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“…This is an important observation in light of a recent report, using a neurokinin B-specific RIA demonstrating the absence of the neuropeptide from rodent intestine [21]. Neurokinin B has been postulated as the endogenous ligand of the pharmacologically-defined neurokinin-3 receptor which appears to mediate tachykinin effects on mammalian enteric neurons [22].…”

Section: Resultsmentioning

confidence: 76%

Neurokinin‐immunoreactivity in human neuroblastomas

McGregor¹,

Gaedicke

Voigt³

1990

FEBS Letters

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Factors regulating differentiation of the peripheral nervous system (PNS) have been widely studied in neuroblastomas which are tumors of the PNS. Five neuroblastomas were investigated for their content of tachykinin neuropeptides, which arise from two distinct genes which appear differentially expressed in the PNS. Radioimmunoassay and column chromatography revealed large amounts of neurokinin B in three of these tumors and the absence of substance P, neurokinin A, neuropeptide K and neuropeptide y from all five tumors. This suggests that neuroblastomas can selectively express the preprotachykinin (PPT) II gene and that they may be valuable for investigating the factors involved in the regulation of these two structurally-related neuropeptide genes.

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Neurokinin B is a preferred agonist for a neuronal substance P receptor and its action is antagonized by enkephalin.

Cited by 155 publications

References 24 publications

Molecular characterisation, expression and localisation of human neurokinin‐3 receptor

Molecular characterisation, expression and localisation of human neurokinin‐3 receptor

Reactive oxygen species are second messengers of neurokinin signaling in peripheral sensory neurons

Neurokinin‐immunoreactivity in human neuroblastomas

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