Neurotransmitter functions of mammalian tachykinins.

Otsuka, Masanori; Yoshioka, Koichi

doi:10.1152/physrev.1993.73.2.229

Cited by 1,015 publications

(626 citation statements)

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“…Activation of SP receptors leads to postsynaptic excitation via G-protein-coupled SP receptors, which stimulate phospholipase C and adenylate cyclase (Mitsuhashi et al, 1992;Otsuka and Yoshioka, 1993;Takeda et al, 1992). Our finding that fear-potentiated startle could be blocked by infusing an SP receptor antagonist into the BLA suggests that SP receptor activation contributes to or is required for activation of BLA projection neurons.…”

Section: Discussionmentioning

confidence: 80%

Effects of Substance P in the Amygdala, Ventromedial Hypothalamus, and Periaqueductal Gray on Fear-Potentiated Startle

Zhao

Yang

Walker

et al. 2008

Neuropsychopharmacol

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The neural pathways through which substance P (SP) influences fear and anxiety are poorly understood. However, the amygdala, a brain area repeatedly implicated in fear and anxiety processes, is known to contain large numbers of SP-containing neurons and SP receptors. Several studies have implicated SP neurotransmission within the amygdala in anxiety processes. In the present study, we evaluated the effects of site-specific infusions of an SP receptor antagonist, GR 82334, on conditioned fear responses using the fear-potentiated startle paradigm. GR 82334 infusion into the basolateral (BLA) or the medial (MeA) nuclei of the amygdala, but not into the central nucleus of the amygdala (CeA), dose dependently reduced fear-potentiated startle. Similar effects were obtained with GR 82334 infusion into the ventromedial nucleus of the hypothalamus (VMH), to which the MeA projects, and into the rostral dorsolateral periaqueductal gray (PAG), to which the VMH projects, but not into the deep layers of the superior colliculus/deep mesencephalic nucleus (dSC/DpMe), an output of the CeA previously shown to be important for fear-potentiated startle. Consistent with previous findings, infusion of the AMPA receptor antagonist, NBQX, into the dSC/DpMe, but not into the PAG, did disrupt fear-potentiated startle. These findings suggest that multiple outputs from the amygdala play a critical role in fear-potentiated startle and that SP plays a critical, probably modulatory role, in the MeA to VMH to PAG to the startle pathway based on these and data from others.

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Section: Discussionmentioning

confidence: 80%

Effects of Substance P in the Amygdala, Ventromedial Hypothalamus, and Periaqueductal Gray on Fear-Potentiated Startle

Zhao

Yang

Walker

et al. 2008

Neuropsychopharmacol

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“…Their biological actions are mediated via the activation of three receptors: the tachykinin NK 1 , tachykinin NK 2 , and tachykinin NK 3 receptors (Regoli et al, 1994). While tachykinin NK 1 and tachykinin NK 3 receptors are widely distributed in the CNS, the tachykinin NK 2 receptor is found centrally with considerably lower levels (Maggi, 1995;Otsuka and Yoshioka, 1993). All three types of tachykinin receptors are located in brain areas implicated in the control of fear and anxiety, such as the hypothalamus, amygdala, hippocampus, and periaqueductal gray matter (Otsuka and Yoshioka, 1993).…”

Section: Effects Of Tachykinin Receptor Ligands In the Mouse Defense mentioning

confidence: 99%

“…While tachykinin NK 1 and tachykinin NK 3 receptors are widely distributed in the CNS, the tachykinin NK 2 receptor is found centrally with considerably lower levels (Maggi, 1995;Otsuka and Yoshioka, 1993). All three types of tachykinin receptors are located in brain areas implicated in the control of fear and anxiety, such as the hypothalamus, amygdala, hippocampus, and periaqueductal gray matter (Otsuka and Yoshioka, 1993). The neuroanatomical distribution of tachykinin receptors has led to numerous studies that investigated the behavioral action of tachykinin receptor ligands in animal models of anxiety (Griebel, 1999b).…”

Section: Effects Of Tachykinin Receptor Ligands In the Mouse Defense mentioning

confidence: 99%

The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic

Blanchard

Griebel

Blanchard

2003

European Journal of Pharmacology

256

159

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The Mouse Defense Test Battery was developed from tests of defensive behaviors in rats, reflecting earlier studies of both acute and chronic responses of laboratory and wild rodents to threatening stimuli and situations. It measures flight, freezing, defensive threat and attack, and risk assessment in response to an unconditioned predator stimulus, as well as pretest activity and postthreat (conditioned) defensiveness to the test context. Factor analyses of these indicate four factors relating to cognitive and emotional aspects of defense, flight, and defensiveness to the test context. In the Mouse Defense Test Battery, GABA A -benzodiazepine anxiolytics produce consistent reductions in defensive threat/attack and risk assessment, while panicolytic and panicogenic drugs selectively reduce and enhance, respectively, flight. Effects of GABA A -benzodiazepine, serotonin, and neuropeptide ligands in the Mouse Defense Test Battery are reviewed. This review suggests that the Mouse Defense Test Battery is a sensitive and appropriate tool for preclinical evaluation of drugs potentially effective against defense-related disorders such as anxiety and panic. D

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“…For the binding experiment, the medium was changed to the assay buffer A of the following composition: 50 mM Tris-HCl (pH 7.4), 150 mM NaCl, 3 mM MnCl 2 , 0.02% BSA, 40 µg / ml bacitracin, 4 µg / ml chymostatin, 4 µg/ ml phosphoramidon, and 4 µg / ml leupeptin. The binding assay for NK 1 The incubation was terminated by vacuum filtration onto a GF / C glass filter presoaked in 0.3% polyethylenimine. The radioactivity on the filter was measured by a liquid scintillation counter.…”

Section: Tachykinin Nk 1 Receptor Bindingmentioning

confidence: 99%

“…The mammalian tachykinins (substance P, neurokinin A, and neurokinin B) are widely distributed throughout the central and peripheral nervous systems, where they act as neurotransmitters or neuromodulators (1,2). Three types of G-protein-coupled receptors, denoted NK 1 , NK 2 , and NK 3 , mediate a wide range of biological activities of tachykinins.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Characterization of T-2328, 2-Fluoro-4'-methoxy-3'-[[[(2S,3S)-2-phenyl-3-piperidinyl]amino]methyl]-[1,1'-biphenyl]-4-carbonitrile Dihydrochloride, as a Brain-Penetrating Antagonist of Tachykinin NK1 Receptor

Watanabe¹,

Asai²,

Ishii³

et al. 2008

J Pharmacol Sci

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Abstract. The pharmacological properties of T-2328 were evaluated as an antagonist of the tachykinin neurokinin 1 (NK 1 ) receptor. T-2328 inhibited the specific binding of [ 3 H][Sar 9 ,Met(O 2 ) 11 ]substance P to tachykinin NK 1 receptors in human lymphoblastic IM9 cells with K i of 0.08 nM. In the same assay, K i for aprepitant, a brain-penetrating NK 1 antagonist, was 1.3 nM. The antagonism of T-2328 is highly selective for the human NK 1 receptors since the affinities for human NK 2 , NK 3 receptors, and 13 other kinds of receptors and ion channels were >1000-fold lower than for NK 1 receptors. Reduction in Bmax with no change in affinity suggests the non-competitive nature of T-2328 interaction with the NK 1 receptor. T-2328 (0.03 -0.1 mg / kg, i.v.) and aprepitant (1 -3 mg / kg, i.v.) significantly prevented the GR73632 (i.c.v.)-induced foot tapping response in gerbils. The potencies of T-2328 in both in vitro and in vivo studies were more than 10 times greater than those of aprepitant. I.v. administration of T-2328 (0.1 -0.3 mg/ kg) potently blocked both acute and delayed emetic responses induced by cisplatin (5 mg / kg, i.p.) in ferrets. It is concluded that T-2328 is a potent, centrally active NK 1 antagonist. T-2328 may have potential as a novel therapeutic agent for the treatment of chemotherapyinduced emesis.

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Neurotransmitter functions of mammalian tachykinins.

Cited by 1,015 publications

References 0 publications

Effects of Substance P in the Amygdala, Ventromedial Hypothalamus, and Periaqueductal Gray on Fear-Potentiated Startle

Effects of Substance P in the Amygdala, Ventromedial Hypothalamus, and Periaqueductal Gray on Fear-Potentiated Startle

The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic

Pharmacological Characterization of T-2328, 2-Fluoro-4'-methoxy-3'-[[[(2S,3S)-2-phenyl-3-piperidinyl]amino]methyl]-[1,1'-biphenyl]-4-carbonitrile Dihydrochloride, as a Brain-Penetrating Antagonist of Tachykinin NK1 Receptor

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