Tachykinin NK2 receptors facilitate acetylcholine release from guinea-pig isolated trachea

D׳Agostino, Gianluigi; Erbelding, Doris; Kilbinger, H.

doi:10.1016/s0014-2999(00)00199-0

Cited by 14 publications

(5 citation statements)

References 11 publications

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“…The present findings contrast with data from a recently published study in which it was shown that tachykinin NK 2 receptors are involved in the facilitation of acetylcholine release from guinea pig trachea [25]. These differing results may be the consequence of species specificity or due to limitations of the experimental methods used.…”

Section: Discussioncontrasting

confidence: 99%

Modulatory role of tachykinin NK₁receptor in cholinergic contraction of mouse trachea

Tournoy

Swert

Leclere³

et al. 2003

Eur Respir J

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Section: Discussioncontrasting

confidence: 99%

Modulatory role of tachykinin NK₁receptor in cholinergic contraction of mouse trachea

Tournoy

Swert

Leclere³

et al. 2003

Eur Respir J

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“…In fact, although there is little direct evidence showing that TKs acting through NK2 receptors enhance acetylcholine release during peristalsis, several results converge to indicate that some of the motor effects of NK2 receptor agonists are atropine‐sensitive. One piece of direct evidence that TKs enhance acetylcholine release through the stimulation of NK2 receptors has been obtained in guinea‐pig airways ( D'Agostino et al , 2000 ). Low doses of NKA have also been shown to enhance rat small‐intestine transit in an atropine‐sensitive manner (Holzer, 1985), and part of the contractile effect induced by NKA in rat, cat, and human isolated colonic muscle is decreased by atropine ( Chang et al , 1991 ; Hellstrom et al , 1991 ; Kolbel et al , 1994 ).…”

Section: Role Of Nk2 Receptors In the Control Of Intestinal Motility:mentioning

confidence: 99%

Tachykinin NK2 receptor antagonists for the treatment of irritable bowel syndrome

Lecci

Capriati

Maggi

2004

British J Pharmacology

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Tachykinin NK2 receptors are expressed in the gastrointestinal tract of both laboratory animals and humans. Experimental data indicate a role for these receptors in the regulation of intestinal motor functions (both excitatory and inhibitory), secretions, inflammation and visceral sensitivity. In particular, NK2 receptor stimulation inhibits intestinal motility by activating sympathetic extrinsic pathways or NANC intramural inhibitory components, whereas a modulatory effect on cholinergic nerves or a direct effect on smooth muscle account for the NK2 receptor-mediated increase in intestinal motility. Accordingly, selective NK2 receptor antagonists can reactivate inhibited motility or decrease inflammation-or stress-associated hypermotility. Intraluminal secretion of water is increased by NK2 receptor agonists via a direct effect on epithelial cells, and this mechanism is active in models of diarrhoea since selective antagonists reverse the increase in faecal water content in these models. Hyperalgesia in response to intraluminal volume signals is possibly mediated through the stimulation of NK2 receptors located on peripheral branches of primary afferent neurones. NK2 receptor antagonists reduce the hyper-responsiveness that occurs following intestinal inflammation or application of stressful stimuli to animals. Likewise, NK2 receptor antagonists reduce intestinal tissue damage induced by chemical irritation of the intestinal wall or lumen. In healthy volunteers, the selective NK2 antagonist nepadutant reduced the motility-stimulating effects and irritable bowel syndrome-like symptoms triggered by intravenous infusion of neurokinin A, and displayed other characteristics that could support its use in patients. It is concluded that blockade of peripheral tachykinin NK2 receptors should be considered as a viable mechanism for decreasing the painful symptoms and altered bowel habits of irritable bowel syndrome patients.

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“…In addition to mediating transmission between primary afferent neurons and peripheral target organs or second order neurons in the CNS, neurokinins may also act on autoreceptors on afferent nerve terminals to regulate terminal excitability (Wen and Morrison 1996) or transmitter release (D'Agostino et al 2000;Malcangio and Bowery 1999). Neurokinin autoreceptors are thought to be linked through G proteins to protein kinase C (and/or other protein kinases), which in turn can phosphorylate and modulate Ca 2ϩ channels (Hall et al 1995;Harding et al 1999;Murase et al 1989;Schmid et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Protein Kinase C Is Involved in Neurokinin Receptor Modulation of N- and L-Type Ca²⁺ Channels in DRG Neurons of the Adult Rat

Sculptoreanu

Groat

2003

Journal of Neurophysiology

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Whole cell patch-clamp techniques were used to examine neurokinin receptor modulation of Ca2+ channels in small to medium size dorsal root ganglia neurons (<40 pF) that express mainly N- and L-type Ca2+ currents. Low concentrations of substance P enhanced Ca2+ currents (5-40%, <0.2 microM), while higher concentrations applied cumulatively reversed these enhancements (5-28% reductions, >0.5 microM). This apparent inhibition by high concentrations of substance P was blocked by the administration of the NK3 antagonist SB 235,375 (0.2 microM). The NK1 agonist, [Sar9,Met11]-substance P (0.05 to 1.0 microM) did not alter Ca2+ currents; whereas the NK2 agonist, [betaAla8]-neurokinin A (4-10), enhanced Ca2+ currents (5-36% increase, 0.05-0.5 microM). The enhancement was reversed by the NK2 antagonist MEN 10,376 (0.2 microM) but unaffected by the NK3 antagonist SB 235,375 (0.2 microM). The NK3 agonist [MePhe7]-neurokinin B (0.5-1.0 microM) inhibited Ca2+ currents (6-24% decrease). This inhibition was not prevented by the NK2 antagonist MEN 10,376 (0.2 microM) but was blocked by the NK3 antagonist SB 235,375 (0.2 microM). Both the enhancement and inhibition of Ca2+ currents by neurokinin agonists were reversed by the protein kinase C inhibitor bisindolylmaleimide I HCl (0.2-0.5 microM). Following inhibition of Ca2+ channels by [MePhe7]-neurokinin the facilitatory effect of BayK 8644 (5 microM) was increased and the inhibitory effect of the N-type Ca2+ channel blocker w -conotoxin GVIA (1 microM) was diminished, suggesting that the NK3 agonist inhibits N-type Ca2+ channels. Similarly, block of all but N-type Ca2+ channels, revealed that [betaAla8]-neurokinin A (4-10) enhanced the currents while [MePhe7]-neurokinin B inhibited the currents. Inhibition of all but L-type Ca2+ channels, revealed that [betaAla8]-neurokinin A (4-10) enhanced the currents while [MePhe7]-neurokinin B had no effect. Activation of protein kinase C with low concentrations of phorbol-12,13-dibutyrate enhanced Ca2+ currents, but high concentrations inhibited N- and L-type Ca2+ currents. In summary, these data suggest that in adult rat dorsal root ganglia neurons, NK2 receptors enhance both L- and N-type Ca2+ channels and NK3 receptors inhibit N-type Ca2+ channels and that these effects are mediated by protein kinase C phosphorylation of Ca2+ channels.

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Tachykinin NK2 receptors facilitate acetylcholine release from guinea-pig isolated trachea

Cited by 14 publications

References 11 publications

Modulatory role of tachykinin NK₁receptor in cholinergic contraction of mouse trachea

Modulatory role of tachykinin NK₁receptor in cholinergic contraction of mouse trachea

Tachykinin NK2 receptor antagonists for the treatment of irritable bowel syndrome

Protein Kinase C Is Involved in Neurokinin Receptor Modulation of N- and L-Type Ca²⁺ Channels in DRG Neurons of the Adult Rat

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Tachykinin NK2 receptors facilitate acetylcholine release from guinea-pig isolated trachea

Cited by 14 publications

References 11 publications

Modulatory role of tachykinin NK1receptor in cholinergic contraction of mouse trachea

Modulatory role of tachykinin NK1receptor in cholinergic contraction of mouse trachea

Tachykinin NK2 receptor antagonists for the treatment of irritable bowel syndrome

Protein Kinase C Is Involved in Neurokinin Receptor Modulation of N- and L-Type Ca2+ Channels in DRG Neurons of the Adult Rat

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Product

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Modulatory role of tachykinin NK₁receptor in cholinergic contraction of mouse trachea

Modulatory role of tachykinin NK₁receptor in cholinergic contraction of mouse trachea

Protein Kinase C Is Involved in Neurokinin Receptor Modulation of N- and L-Type Ca²⁺ Channels in DRG Neurons of the Adult Rat