Disease relevance of NEUROKININ A

• Neurogenic inflammation, which results from peripheral release of substance P and neurokinin A, is almost absent in the mutant mice [1].
• Substance P/neurokinin A-encoding mRNAs are expressed in neurons within the myenteric plexus of the esophagus and stomach, being more numerous in the latter, and in ganglion cells distributed to both the myenteric and submucosal plexuses of the intestine [2].
• CONCLUSIONS: Plasma NKA is an accurate marker of prognosis for midgut carcinoid tumours [3].
• Factors associated with a poor outcome on univariate analysis included: plasma neurokinin A (NKA), urinary 5-hydroxyindolacetic acid output, age, and >/=5 liver metastases [3].
• Nedocromil sodium has prevented the edema in human skin induced by substance P and neurokinin A, and, in the isolated rabbit trachea, has prevented substance P-induced potentiation of cholinergic neural responses at preganglionic (but not postganglionic) sites [4].

Psychiatry related information on NEUROKININ A

• The effects of capsaicin, substance P (SP) and neurokinin A (NKA) on motor activity and vascular permeability was investigated in the rat lower urinary tract (bladder dome and neck, proximal urethra and ureters) [5].
• NKA also reduced reflex response latency in tail-flick and hot plate tests [6].
• Neurokinin A in carcinoid tumours has an N-terminal heterogeneity; this multiplicity constitutes a further support for the hypothesis that carcinoid tumours produce a number of tachykinins which may be present in different relative amounts in individual patients and may contribute to the individual differences in symptomatology [7].
• The effects of intracerebroventricular injections of the neurokinin-2 (NK-2) receptor agonist neurokinin A and the neurokinin-3 (NK-3) receptor agonist senktide on scopolamine (sc)-induced amnesia were investigated based on spontaneous alternation performance in mice [8].

High impact information on NEUROKININ A

• Counterparts of skin tachykinins in mammalian tissues are SP, neurokinin A, and neurokinin B [9].
• Intravenous calcitonin gene-related peptide (CGRP) and neurokinin A markedly elicited gastric mucus secretion, as did substance P to a lesser extent [10].
• Electrically evoked nonadrenergic noncholinergic contractions of isolated bronchi mediated by the release of neurokinin A (NKA) from C-fibers, but not those elicited by exogenous NKA, were inhibited by NS1619 [11].
• Substance P (SP), neurokinin A (NKA), and calcitonin gene-related peptide (CGRP) have potent proinflammatory effects in the airways [12].
• Neurokinin A (1 microM) or B was without effect, implicating NK1 tachykinin receptors [13].

Chemical compound and disease context of NEUROKININ A

• 2. Seven minutes following the intraperitoneal injection of capsaicin (10 mg/kg body weight) plasma CGRP and neurokinin A levels were found to rise by 15- and 4-fold respectively, while there was no change in circulating calcitonin levels [14].
• In Fura 2-AM-loaded ulcerative colitis HSCM cells, neurokinin A- and caffeine-induced peak Ca(2+) increase and cell shortening were significantly reduced [15].
• Finally, the hyperalgesia produced by sustained noxious thermal stimulation of the tip of the tail was unaffected by intrathecal administration of SR 48968; thus, it remains to find a physiological response in which endogenous neurokinin A and NK2 receptors at the spinal level are involved in the rat in vivo [16].
• Airway hyper-responsiveness to neurokinin A and bradykinin following Mycoplasma pneumoniae infection associated with reduced epithelial neutral endopeptidase [17].
• Pretreatment of the cells with pertussis toxin (500 ng/ml for 18 h) did not significantly modify the basal or stimulated phosphatidylinositol turnover but reduced the basal and NKA-induced PGE2 release by about 35% [18].

Biological context of NEUROKININ A

• Both substance P and neurokinin A modify water and ion transport in vivo [19].
• Moreover, the distribution of 125I-labeled gamma-PPT-(72-92)-NH2 and 125I-labeled neurokinin A binding sites are very similar in rat brain [20].
• A rat salivation bioassay was used to demonstrate potent effects of NPK at low doses, while effects due to NKA were much weaker at higher doses [21].
• CGRP was shown to increase both cell number and DNA synthesis, whereas NKA, NPY, and VIP were ineffective [22].
• Synthetic oligonucleotides were used to screen a rat striatal cDNA library for sequences corresponding to the tachykinin peptides substance P and neurokinin A [23].

Anatomical context of NEUROKININ A

• Whereas no evidence of local tachykinin biosynthesis was found 12 h after challenge, increased levels of preprotachykinin (PPT)-A mRNA (encoding SP and NKA) were found in nodose ganglia [12].
• In the rodent stomach, these local regulatory roles of sensory neurons are mediated by calcitonin gene-related peptide acting via calcitonin gene-related peptide 1 receptors and neurokinin A acting via neurokinin 2 receptors, with both peptides using nitric oxide as their common messenger [24].
• Expression of substance P/neurokinin A-encoding preprotachykinin messenger ribonucleic acids in the rat enteric nervous system [2].
• Submucosal blood vessels of the mammalian stomach are densely innervated by neurons containing calcitonin gene-related peptide (CGRP), substance P, neurokinin A, and vasoactive intestinal polypeptide (VIP) [25].
• Induction of negative hematopoietic regulators by neurokinin-A in bone marrow stroma [26].

Associations of NEUROKININ A with other chemical compounds

• In the airways, a three- to fourfold increase of SP, NKA, and CGRP, was seen 24 h following allergen challenge [12].
• In mammals, three of these peptides (substance P, neurokinin A and neurokinin B) satisfy the criteria to be considered as neurotransmitters either in the central, peripheral or enteric nervous systems [27].
• Neonatal capsaicin pretreatment did not attenuate SP- nor NKA-induced effects in the dura and actually increased extravasation in the conjunctiva [28].
• Site-directed mutagenesis was used to alter these residues in order to ascertain their importance in binding neurokinin A (NKA), the physiological peptide ligand for the NK2 receptor, and the non-peptide NK2 receptor selective antagonist SR48968 [29].
• When activated, truncated receptors mediate stronger and more prolonged phosphoinositide hydrolysis than wild-type receptor; however, the amplitude and kinetics of the NKA-induced rise in cytosolic Ca2+ remain unaltered [30].

Gene context of NEUROKININ A

• These results indicate that the reduction of seizure activity and the neuroprotection observed in preprotachykinin A null mice are caused by the extinction of a SP/neurokinin A-mediated signaling pathway that is activated by seizures [31].
• The NK1 receptor couples to both G(s) and G(q/11), resides on the plasma membrane, and mediates rapid ERK1/2 activation and nuclear translocation in response to neurokinin A [32].
• The only Ci-TK receptor, Ci-TK-R, was equivalently activated by Ci-TK-I, SP, and neurokinin A at physiological concentrations, whereas Ci-TK-II showed 100-fold less potent activity, indicating that the ligand selectivity of Ci-TK-R is distinct from those of vertebrate TK receptors [33].
• Pharmacological characterization of cloned human NK-2 (neurokinin A) receptor expressed in a baculovirus/Sf-21 insect cell system [34].
• The spinal cord, striatum, or both were used for the quantification of tachykinin [SP and neurokinin A (NKA)] and opioid peptides [[Met5]-enkephalin (ME) and dynorphin A (1-8) (DYN)] by radioimmunoassays [35].

Analytical, diagnostic and therapeutic context of NEUROKININ A

• The cellular localization of substance P/neurokinin A-encoding preprotachykinin mRNAs in the rat enteric nervous system was studied by means of in situ hybridization histochemistry using 35S- or 3H-labeled single-stranded ribonucleic acid (RNA) probes which recognize all three preprotachykinin mRNA species, alpha, beta, and gamma [2].
• Two types of cDNAs were isolated and defined by restriction enzyme analysis and DNA sequencing to encode both substance P and neurokinin A [23].
• Two mammalian tachykinins, substance P (SP) and neurokinin A (NKA), were measured by radioimmunoassay in canine cephalic blood vessels and tested for their vasoactivity in vitro [36].
• The ligand binding site of the neurokinin 2 receptor. Site-directed mutagenesis and identification of neurokinin A binding residues in the human neurokinin 2 receptor [29].
• Neurokinin-A in bone and joint tissues: changes in adjuvant arthritis [37].

References