Disease relevance of Tacr3

• A decrease in cytoplasmic NK3-R immunoreactivity was observed within 15 min of hypotension [1].
• These results suggest that activation of spinal NK1R and NK2R, presumably by their endogenous ligands (substance P and neurokinin A), maintain visceral hyperalgesia and support the notion that activation of NK3R (presumably by neurokinin B) is pronociceptive [2].
• The present results suggest that NK3 receptor-active peptides might be symptom inducers in oral dyskinesia [3].
• These results indicate that peripheral NK3 receptor antagonism reduced nociception associated with CRD and hypersensitivity induced by stress but not inflammation [4].
• The microinjection of 1-10 ng of suc-[Asp5, Me-Phe8]-SP(6-11) (senktide, a selective neurokinin B receptor peptide) into the NTS caused long-lasting hypertension and tachycardia [5].

Psychiatry related information on Tacr3

• We investigated and compared the effects of two amphibian tachykinins, the NK1 receptor agonist PG-SPI and the NK3 receptor agonist PG-KII, and the mammalian tachykinins substance P, neurokinin A and neurokinin B on the reaction time to a painful radiant heat stimulus (tail-flick test in rats) after intracerebroventricular injection [6].
• The NK-3 receptor agonists, senktide and DiMe-C7, as well as the endogenous NK-2 receptor ligand, NKA, produced dose-dependent increases in locomotor activity [7].

High impact information on Tacr3

• The results indicated that selection in WGA after mutagenic treatment of a metastatic parental tumor cell line (MDAY-D2), which was M phi-sensitive (M phi S) and NK-resistant (NKR), can result in the isolation of a significantly M phi-resistant (M phi R) and NK-sensitive (NKS) tumor variant, MDW4 [8].
• Results: Cholera toxin-induced water and electrolyte secretion was inhibited by the substance P antagonists and the NK-1 and NK-2 receptor antagonists, but not by the NK-3 receptor antagonist or by pretreatment with capsaicin [9].
• RESULTS: In awake rats, intraperitoneal administration of the NK3-receptor antagonist SR 142,801 reduced, whereas the NK3-receptor agonist senktide increased, both the rectocolonic inhibitory reflex and abdominal contractions produced by colorectal distention [10].
• In cells coexpressing both receptors, prior activation of the NK1R inhibited endocytosis and homologous desensitization of the NK3R, which was dose-dependently reversed by overexpression of beta-ARR1 [11].
• Thus, the high-affinity and prolonged interaction of the NK1R with beta-ARRs depletes beta-ARRs from the cytosol and limits their role in desensitization and endocytosis of the NK3R [11].

Chemical compound and disease context of Tacr3

• When hypotension was induced with hydralazine, NK3-R internalization was observed within 5 min (p < 0.005) [1].
• NK3 receptor blockade prevents hyperalgesia and the associated spinal cord substance P release in monoarthritic rats [12].
• The increases in NK-3R mRNA in the cerebellum point to the development of receptor supersensitivity and suggest a functional role of NKB in this animal model of epilepsy [13].
• This study was designed to determine whether NK3 receptor antagonists crossing (talnetant) or not (SB-235375) the blood-brain barrier reduce the nociceptive response to colo-rectal distension (CRD) and whether NK3 antagonism reduces inflammation- or stress-induced hypersensitivity to rectal distension [4].

Biological context of Tacr3

• We compared the colocalization of NK1R and NK3R with beta-arrestins 1 and 2, which play major roles in receptor desensitization, endocytosis, and signaling [14].
• Functional cDNA clones for rat neuromedin K receptor were isolated from a rat brain cDNA library by cross-hybridization with the bovine substance K receptor cDNA [15].
• In tissue obtained from estrogen-dominated rats (ovariectomized estrogen-treated rats and rats in estrus), the magnitude of uterine contractions decreased in response to consecutive additions of the NK3-R-selective agonist senktide [16].
• The NKA-evoked gastric contraction is also primarily due to NK2 receptor activation, whereas the NKA-induced vasoconstriction is mediated by a distinct and unusual type of NK2-like receptor that is blocked by a combination of NK1, NK2 and NK3 receptor antagonists only [17].
• Effects of the peripherally acting NK receptor antagonist, SB-235375, on intestinal and somatic nociceptive responses and on intestinal motility in anaesthetized rats [18].

Anatomical context of Tacr3

• In contrast, the NK3R interacted transiently with only beta-arrestin 2 at the plasma membrane [14].
• The NK3 receptor agonist [MePhe7]-neurokinin B produced no change in blood flow in normal or in inflamed rat knee joints (n = 7 and 5, P > 0.05) [19].
• Localization of the neuromedin K receptor (NK3) in the central nervous system of the rat [20].
• The expression of NKR was indicated on neuronal cell bodies and dendrites [20].
• In contrast, NKR mRNA is predominantly expressed in the nervous system, particularly in the cortex, hypothalamus and cerebellum, whereas SKR mRNA expression is restricted to the peripheral tissues, being abundant in the urinary bladder, large intestine, stomach and adrenal gland [21].

Associations of Tacr3 with chemical compounds

• E2 treatment decreased by 15-fold NK3R mRNA [22].
• This stimulated effect of substance P was antagonized by the NK1--receptor antagonist (5 x 10(-7) M), but not by the NK3-receptor antagonist (5 x 10(-7) M) [23].
• The stimulant effect of PG-KII on guinea pig acini was significantly reduced by the NK3-receptor antagonist, SR 142801 (5 x 10(-7) M), and left unchanged by the NK1-receptor antagonist, SR 140333 (5 x 10(-7) M) [23].
• In this paper we investigated and compared the effect of PG-KII (10(-9) to 10(-6) M), a natural NK3-receptor agonist, with that of the known secretagogues substance P (10(-9) to 10(-6)M), caerulein (10(-11) to 10(-8) M) and carbachol (10(-8) to 10(-5) M), on amylase secretion from dispersed pancreatic acini of the guinea pig and rat [23].
• In the current study, we furthered our investigations of the role of estrogen in the regulation of NK3-R-mediated myometrial contractility [16].

Regulatory relationships of Tacr3

• We show that the functional antagonism of dynorphin at the NK4 receptor is reversed by the non-specific opioid antagonist naloxone and that tachykinin-evoked responses at the NK4 receptor are inhibited by the non-peptide NK3 receptor antagonist SR142801 in a concentration dependent manner [24].
• Neurokinin B receptor (NK3)-containing neurons in the paraventricular and supraoptic nuclei of the rat hypothalamus synthesize vasopressin and express Fos following intravenous injection of hypertonic saline [25].
• More than 90% of NK3 receptor-expressing neurons in the basal forebrain region showed signals for glutamate decarboxylase mRNA, indicating that almost all NK3 receptor-expressing neurons were gamma-aminobutyric acid (GABA)ergic neurons [26].

Other interactions of Tacr3

• The NK1R resensitized greater than twofold more slowly than the NK3R [14].
• Thus, although these studies do not identify SP as the NK3-R ligand, they do provide evidence for hypotension-induced release of an endogenous tachykinin in SON and evidence suggesting a role for NK3-Rs in transcription regulation [1].
• The present study demonstrated that a large proportion of neurokinin B receptor-like immunoreactive neurons in the paraventricular hypothalamic and supraoptic nuclei contained vasopressin-like immunoreactivity, and expressed Fos-like immunoreactivity after intravenous administration of hypertonic saline [25].
• Neurons showing both neuromedin K receptor-like and choline acetyltransferase immunoreactivities were hardly detected in other aforementioned regions of the forebrain, brainstem and spinal cord [27].
• The upregulation of NF-kappaB and ICAM-1 was attenuated by NK receptor antagonist and antioxidants [28].

Analytical, diagnostic and therapeutic context of Tacr3

• The distribution of the neuromedin K receptor (NK3; NKR) in the central nervous system was investigated in the adult rat by using in situ hybridization and immunohistochemical techniques [20].
• 3. Intra-articular perfusion of the selective NK receptor agonist [Nle10]-neurokinin A4-10 (0.8 nmol min-1) and the selective NK3 receptor agonist [MePhe7]-neurokinin B (0.8 nmol min1) produced no increase in plasma extravasation in normal or in inflamed rat knee joints (n = 4 and 11, P > 0.05) [19].
• By using a double immunofluorescence method we examined the distribution of noradrenergic neurons expressing substance P receptor (NK1) or neuromedin K receptor (NK3) in the rat brainstem [29].
• 5. It is concluded that by the use of neurokinin receptor-selective agonists, subpopulations of spinal cord neurones in primary dissociated cell culture can be differentiated which express the NK1 or the NK3 receptor [30].
• Differential effects of intraventricular injections of tachykinin NK1 and NK3 receptor agonists on normal and sham drinking of NaCl by sodium-deficient rats [31].

References