Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P21452 (NK-2 receptor)
 180 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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. Spontaneous alternation performance is based on spatial working memory which produces a natural tendency to explore a less recently visited arm in a Y-maze. Neurokinin A (0.1-3 micrograms) or senktide (0.0003-0.03 microgram) alone did not influence either spontaneous alternation performance or total arm entries. However, neurokinin A (0.3 and 1 microgram) and senktide (0.003 and 0.03 microgram) inhibited the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance without affecting the scopolamine (1 mg/kg)-induced increase in total arm entries. Although the effects of neurokinin A (0.3 microgram) on the scopolamine-induced impairment of spontaneous alternation performance were almost completely antagonized by pretreatment with the NK-2 receptor antagonist cyclo (Gln-Trp-Phe-Gly-Leu-Met) (1 microgram), the inhibitory effects of senktide (0.003 microgram) were not influenced by pretreatment with the NK-3 receptor antagonist [Trp7, beta-Ala8]neurokinin A-(4-10). These findings suggest that neurokinin A inhibits the scopolamine-induced impairment of spontaneous alternation performance associated with working memory through the mediation of tachykinin NK-2 receptors, while senktide has some pharmacological action other than its effects on NK-3 receptors.
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PMID:Neurokinin A and senktide attenuate scopolamine-induced impairment of spontaneous alternation performance in mice. 890 97

Several small molecule non-peptide antagonists of the NK-1 and NK-2 receptors have been developed. Mutational analysis of the receptor protein sequence has led to the conclusion that the binding site for these non-peptide antagonists lies within the bundle created by transmembrane domains IV-VII of the receptor and differs from the binding sites of peptide agonists and antagonists. The current investigation uses site-directed mutagenesis of the NK-1 and NK-2 receptors to elucidate the amino acids that are important for binding and functional activity of the first potent dual NK-1/NK-2 antagonist MDL103,392. The amino acids found to be important for MDL103,392 binding to the NK-1 receptor are Gln-165, His-197, Leu-203, Ile-204, Phe-264, His-265 and Tyr-272. The amino acids found to be important for MDL103,392 binding to the NK-2 receptor are Gln-166, His-198, Tyr-266 and Tyr-289. While residues in transmembrane (TM) domains IV and V are important in both receptors (Gln-165/166 and His-197/198), residues in TM V and VI are more important for the NK-1 receptor and residues in TM VII play a more important role in the NK-2 receptor. These data are the first report of the analysis of the binding site of a dual tachykinin receptor antagonist and indicate that a single compound (MDL103,392) binds to each receptor in a different manner despite there being a high degree of homology in the transmembrane bundles. In addition, this is the first report in which a model for the binding of a non-peptide antagonist to the NK-2 receptor is proposed.
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PMID:The neurokinin-1 and neurokinin-2 receptor binding sites of MDL103,392 differ. 1065 91

Present investigations were undertaken to study the influence of peptide NK-1 and NK-2 receptor agonists and antagonists as well as substance P and neurokinin A (the natural ligands for these tachykinin receptors) on oxytocin (OT) release from isolated rat hypothalamo-neurohypophysial (H-N) system as well as to determine whether the tachykinin NK-1 and/or NK-2 receptors contribute to the response of oxytocinergic neurons to melatonin. The results show, for the first time, that highly selective NK-1 receptor agonist, i.e., [Sar(9),Met(O(2))(11)]-Substance P, enhances while the NK-1 receptor antagonist (Tyr(6),D-Phe(7),D-His(9))-Substance P (6-11) - sendide - diminishes significantly OT secretion; the latter peptide was also found to antagonize the substance P-induced hormone release from isolated rat H-N system, when used at the concentration of 10(-7) M/L. Melatonin significantly inhibited basal and substance P-stimulated OT secretion. Neurokinin A and the NK-2 receptor selective agonist (beta-Ala(8))-Neurokinin A (4-10) as well as the NK-2 receptor antagonist (Tyr(5),D-Trp(6,8,9),Lys-NH(2)(10))-Neurokinin A (4-10) were essentially inactive in modifying OT release from the rat H-N system in vitro. The present data indicate a distinct role for tachykinin NK-1 (rather than NK-2) receptor in tachykinin-mediated regulation of OT secretion from the rat H-N system. Under present experimental conditions, however, a role of respective tachykinin receptors in the response of oxytocinergic neurons to melatonin has not been found.
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PMID:Role of tachykinin receptors and melatonin in oxitocin secretion from isolated rat hypothalmo-neurohypophysial system. 1561 40

The aim of the present study was to investigate the effect of peptide NK-1 and NK-2 receptors agonists and antagonists (and their natural ligands, i.e., substance P and neurokinin A) on the oxytocin (OT) secretion from the rat neurohypophysis into the blood. Intracerebroventricular (icv) injection of substance P (SP) or highly selective NK-1 receptor agonist--[(Sar(9),Met(O2)(11))-Substance P]-- significantly stimulated the OT secretion from the rat neurohypophysis into the general circulation. After icv injection of the NK-1 receptor antagonist--[(Tyr(6),D-Phe(7),D-His(9))-Substance P (6-11)]--the blood plasma OT concentration was significantly lower, when compared to vehicle-injected animals. On the other hand, the icv administered neurokinin A (NKA) and the NK-2 receptor agonist--[(beta-Ala(8))-Neurokinin A (4-10)]--were essentially inactive in modifying OT secretion. However, such injection of the NK-2 receptor antagonist--[(Tyr(5),D-Trp(6,8,9),Lys-NH2(10))-Neurokinin A (4-10)]--was found to diminish the blood plasma hormone concentration, when compared to vehicle-injected animals. The neurohypophysial content of OT was decreased in NKA-treated rats, but neither the NK-2 receptor agonist nor antagonist were able to affect the OT output from the rat posterior pituitary. The hypothalamic levels of OT were not modified by any of the studied peptides. The present data strongly indicate a major role for the tachykinin NK-1 receptor in SP- and/or NKA-dependent regulation of OT secretion from the rat neurohypophysis into the blood.
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PMID:Oxytocin release from the rat neurohypophysis into the blood: effects of tachykinin NK-1 and NK-2 receptors agonists and antagonists. 1895 97


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