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The place of tachykinin NK2 receptor antagonists in the treatment diarrhea-predominant irritable bowel syndrome

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Szymaszkiewicz A., Malkiewicz A., Storr M., Fichna J., Zielinska M.
Journal of Physiology and Pharmacology
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2019
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tom 70
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nr 1
2
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Oxytocin release from the rat neurohypophysis into the blood: effects of tachykinin NK-1 and NK-2 receptors agonists and antagonists

100%
Juszczak M., Boczek-Leszczyk E.
Journal of Physiology and Pharmacology
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2008
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tom 59
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nr 3
553-562
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 - [(Sar9,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 - [(Tyr6,D-Phe7,D-His9)-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 - [(ß-Ala8)-Neurokinin A (4-10)] - were essentially inactive in modifying OT secretion. However, such injection of the NK-2 receptor antagonist - [(Tyr5,D-Trp6,8,9,Lys-NH210)-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.
3
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Role of tachykinin receptors and melatonin in oxytocin secretion from isolated rat hypothalamo-neurohypophysial system

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Juszczak M., Furykiewicz-Nykis K., Stempniak B.
Journal of Physiology and Pharmacology
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2004
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tom 55
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nr 4
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., [Sar9,Met(O2)11]-Substance P, enhances while the NK-1 receptor antagonist (Tyr6,D-Phe7,D-His9)-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 (ß-Ala8)-Neurokinin A (4-10) as well as the NK-2 receptor antagonist (Tyr5,D-Trp6,8,9, Lys-NH210)-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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