Involvement of tachykinin receptors in oedema formation and plasma extravasation induced by substance P, neurokinin A, and neurokinin B in mouse ear

The purpose of this study was to determine the receptor subtype(s) that mediates tachykinin-induced neurogenic plasma extravasation in the hamster cheek pouch. Changes in microvascular clearance were quantified by counting the number of leaky sites and calculating the clearance of fluorescein isothiocyanate-dextran [mol wt 70,000 (Dextran 70)] during suffusion of the cheek pouch with substance P, neurokinin A, neurokinin B, and capsaicin. Suffusion of substance P, capsaicin, and neurokinin A, but not neurokinin B, was associated with a significant concentration-dependent increase in leaky site formation and clearance of fluorescein isothiocyanate-Dextran 70 (P < 0.05). However, the responses to substance P and capsaicin were significantly greater than those to neurokinin A. Pretreatment with the selective, nonpeptide NK1 receptor antagonist, CP-96,345, significantly attenuated substance P- and capsaicin-induced but not neurokinin A-induced responses (P < 0.05). These effects were specific, since the 2R,3R enantiomer, CP-96,344, was inactive, and CP-96,345 had no significant effect on adenosine-induced responses. We conclude that, in the hamster cheek pouch, NK1 receptors are the predominant receptors that mediate neurogenic plasma extravasation.

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Tachykinin receptors in smooth muscles: A study with agonists (substance P, neurokinin A) and antagonists

European Journal of Pharmacology ◽

10.1016/0014-2999(85)90659-4 ◽

1985 ◽

Vol 118 (1-2) ◽

pp. 25-36 ◽

Cited By ~ 47

Author(s):

Jacques Mizrahi ◽

Stéphane Dion ◽

Pedro D'Orléans-Juste ◽

Emanuel Escher ◽

Guy Drapeau ◽

...

Keyword(s):

Substance P ◽

Smooth Muscles ◽

Neurokinin A ◽

Tachykinin Receptors

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Redundancy in the central tachykinin systems safeguards puberty onset and fertility

10.1101/443333 ◽

2018 ◽

Author(s):

Silvia León ◽

Chrysanthi Fergani ◽

Rajae Talbi ◽

Serap Simavli ◽

Caroline A. Maguire ◽

...

Keyword(s):

Substance P ◽

Reproductive Success ◽

Sex Steroids ◽

Delayed Puberty ◽

Neurokinin A ◽

Neurokinin B ◽

Female Mice ◽

Gnrh Release ◽

Lh Release ◽

Puberty Onset

ABSTRACTThe tachykinin neurokinin B (NKB, Tac2) is critical for GnRH release. NKB signaling deficiency leads to infertility in humans. However, some patients reverse this hypogonadism resembling the fertile phenotype of Tac2KO and Tacr3KO (encoding NKB receptor, NK3R) mice despite the absence of NKB signaling. Here, we demonstrate that in the absence of NKB signaling, other tachykinins (substance P and neurokinin A [NKA], encoded by Tac1) may take over to preserve fertility. The complete absence of tachykinins in Tac1/Tac2KO mice leads to delayed puberty onset in both sexes and infertility in 80% of females (but not males), in contrast to the 100% fertile phenotype of Tac1KO and Tac2KO mice separately. Furthermore, we demonstrate that NKA controls puberty onset and LH release through NKB-independent mechanisms in the presence of sex steroids and NKB-dependent mechanisms in their absence. In summary, tachykinins interact in a coordinated manner to ensure reproductive success in female mice.

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NK1 receptors mediate leukocyte adhesion in neurogenic inflammation in the rat trachea

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1995.268.2.l263 ◽

1995 ◽

Vol 268 (2) ◽

pp. L263-L269 ◽

Cited By ~ 8

Author(s):

P. Baluk ◽

C. Bertrand ◽

P. Geppetti ◽

D. M. McDonald ◽

J. A. Nadel

Keyword(s):

Substance P ◽

Hypertonic Saline ◽

Receptor Agonist ◽

Neurogenic Inflammation ◽

Leukocyte Adhesion ◽

Neurokinin A ◽

Plasma Extravasation ◽

Nk1 Receptor ◽

Nk1 Receptors ◽

Plasma Leakage

In neurogenic inflammation, tachykinins trigger the adhesion of neutrophils and eosinophils to leaky venules. The goals of the present study were to determine whether this leukocyte adhesion is mediated by neurokinin type 1 (NK1) receptors and to determine whether the amount of leukocyte adhesion corresponds to the amount of plasma leakage. Anesthetized rats were injected intravenously with substance P, the NK1 receptor agonist [Sar9, Met(O2)11]-substance P, or the NK2 receptor agonist [beta-Ala8]neurokinin A-(4–10). Five minutes later, the adherent neutrophils and eosinophils in blood vessels of the tracheal mucosa were stained histochemically and plasma leakage was quantified, as assessed by the extravasation of Monastral blue. Substance P and the NK1 agonist caused similar amounts of leukocyte adhesion, but the NK2 agonist had no effect. Pretreatment with the NK1 receptor antagonist CP-96,345 (4 mg/kg iv), before challenge with substance P, capsaicin, or aerosol hypertonic saline, reduced the amount of neutrophil adhesion by 56%, 93%, and 57% and reduced the amount of eosinophil adhesion by 70%, 83%, and 65%, respectively. Plasma extravasation was decreased by 89%, 95%, and 94%. The number of adherent neutrophils in the trachea was strongly correlated with the number of adherent eosinophils (r2 = 0.61). The greatest amount of leukocyte adhesion occurred in larger diameter venules than did the maximal amount of Monastral blue leakage. We conclude that NK1 receptors mediate the adhesion of neutrophils and eosinophils as well as the plasma leakage triggered by substance P, capsaicin, or hypertonic saline. This leukocyte adhesion evidently does not occur at exactly the same sites as the plasma leakage.

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Regional distribution of Neuropeptide K and other tachykinins (Neurokinin A, Neurokinin B and substance P) in rat central nervous system

Brain Research ◽

10.1016/0006-8993(86)91514-3 ◽

1986 ◽

Vol 399 (2) ◽

pp. 240-249 ◽

Cited By ~ 173

Author(s):

Heii Arai ◽

Piers C. Emson

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Substance P ◽

Regional Distribution ◽

Neurokinin A ◽

Neurokinin B ◽

Neuropeptide K

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Neurokinin A but not neurokinin B and substance P induces codeine-resistant coughs in awake guinea-pig

Regulatory Peptides ◽

10.1016/0167-0115(92)91009-o ◽

1992 ◽

Vol 37 ◽

pp. S154

Author(s):

K. Takahama ◽

J. Fuchikami ◽

Y. Isohama ◽

H. Kai ◽

T. Miyata

Keyword(s):

Substance P ◽

Guinea Pig ◽

Neurokinin A ◽

Neurokinin B

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Substance P and neurokinin A induced desentization to cardiovascular and behavioral effects: evidence for the involvement of different tachykinin receptors

Brain Research ◽

10.1016/0006-8993(93)90139-e ◽

1993 ◽

Vol 625 (1) ◽

pp. 75-83 ◽

Cited By ~ 19

Author(s):

Juraj Culman ◽

Carsten Tschöpe ◽

Neltje Jost ◽

Keiichi Itoi ◽

Thomas Unger

Keyword(s):

Substance P ◽

Behavioral Effects ◽

Neurokinin A ◽

Tachykinin Receptors

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Expression and cellular localization of substance P/neurokinin A and neurokinin B mRNAs in the rat retina

Visual Neuroscience ◽

10.1017/s095252380000986x ◽

1989 ◽

Vol 3 (6) ◽

pp. 527-535 ◽

Cited By ~ 38

Author(s):

Nicholas C. Brecha ◽

Catia Sternini ◽

Karl Anderson ◽

James E. Krause

Keyword(s):

Substance P ◽

Ganglion Cell ◽

Cellular Localization ◽

Amacrine Cells ◽

Specific Cell ◽

Neurokinin A ◽

Neurokinin B ◽

Rat Retina ◽

Rna Probes

AbstractThe mammalian tachykinin peptides, substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) are encoded by distinct mRNAs derived from separate preprotachykinin (PPT) genes. The SP/NKA-encoding PPT gene generates three mRNAs by alternative RNA processing: α-PPT mRNA, which encodes SP only, and β- and γ-PPT mRNAs, which encode both SP and NKA. The NKB-encoding PPT gene generates mRNAs that produce NKB. The distribution and cellular localization of SP, NKA and NKB mRNAs in the rat retina were studied by RNA blot and in situ hybridization techniques. Blot hybridization analysis of retinal RNA extracts with [32P]-labeled RNA probes complementary to SP/NKA and NKB mRNAs demonstrated single bands of hybridization at 1300 and 900 bases, respectively. Solution hybridization-nuclease protection experiments showed multiple SP/NKA-encoding transcripts with relative levels of ρ-PPT mRNA > β-PPT mRNA ≫ α-PPT mRNA. In situ hybridization histochemistry with [35S]-labeled antisense RNAs demonstrated thatSP/NKA-encoding transcripts are expressed in small-to-medium somata located in the proximal inner nuclear, inner plexiform, and ganglion cell layers, whereas NKB-encoding transcripts are expressed in small-to-medium somata located only in the ganglion cell layer. In this layer, cells containing NKB mRNAs are more numerous than those containing SP/NKA mRNAs. Only background labeling was observed in sections incubated with sense RNA probes, pretreated with RNase A prior to hybridization or incubated in hybridization buffer without the labeled probe. Immunohistochemical studies with a monoclonal antibody directed to the conserved COOH-terminal sequence of the tachykinin peptides revealed tachykinin-like immunoreactive somata with similar size and distribution to those containing SP/NKA- and NKB-encoding transcripts. These results indicate that both SP/NKA and NKB mRNAs are present in the rat retina and that the PPT genes are differentially expressed in specific cell populations. The size and distribution of these cells suggest that they are amacrine and displaced amacrine cells, however, the possibility that tachykinins are present also in ganglion cells in the rat retina cannot be ruled out.

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