NK1 receptors mediate tachykinin-induced increase in microvascular clearance in hamster cheek pouch

1993 ◽  
Vol 265 (2) ◽  
pp. H593-H598
Author(s):  
X. P. Gao ◽  
R. A. Robbins ◽  
R. M. Snider ◽  
J. Lowe ◽  
S. I. Rennard ◽  
...  
Keyword(s):  
Substance P ◽  
Fluorescein Isothiocyanate ◽  
Cheek Pouch ◽  
Neurokinin A ◽  
Plasma Extravasation ◽  
Hamster Cheek Pouch ◽  
Neurokinin B ◽  
Dextran 70 ◽  
Fluorescein Isothiocyanate Dextran ◽  
Neurogenic Plasma Extravasation

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.

Resistance and exchange microvessels are modulated by different PAF receptors

1991 ◽  
Vol 261 (5) ◽  
pp. H1648-H1652 ◽  
Author(s):  
A. C. Tomeo ◽  
W. N. Duran
Keyword(s):  
Platelet Activating Factor ◽  
Fluorescein Isothiocyanate ◽  
Fold Increase ◽  
Cheek Pouch ◽  
Receptor Sensitivity ◽  
Hamster Cheek Pouch ◽  
Vasoconstrictor Response ◽  
Paf Receptor ◽  
Fluorescein Isothiocyanate Dextran ◽  
Arteriolar Diameter

Using several platelet activating factor (PAF) receptor antagonists, we investigated whether a differential receptor sensitivity to PAF exists between the arteriolar and venular segments of the microcirculation. The microvascular bed of the hamster cheek pouch was observed with intravital fluorescent television microscopy. Alterations in arteriolar diameter and in the clearance of fluorescein isothiocyanate-dextran (FITC-Dx 150; mol wt 150,000) were measured in response to PAF. Topical application of 10(-7) M PAF elicits a 10-fold increase in FITC-Dx 150 clearance (mean +/- SE = 9,172 +/- 1,289 nl.2 h-1.g-1) compared with control and vasoconstricts arterioles (20-40 microns) to approximately 50% their control diameters. Pretreatment with WEB 2086 (2 mg/kg iv) or SDZ 63-675 (10 mg/kg iv) blocks PAF-induced vasoconstriction and significantly attenuates the clearance of FITC-Dx 150 evoked by PAF, producing mean clearance values of 2,164 +/- 604 and 3,648 +/- 262 nl.2 h-1.g-1 respectively. L-659,989 (2 or 10 mg/kg iv) and SDZ 63-675 (5 mg/kg iv) abolished the vasoconstrictor response but not the postcapillary venular permeability response to PAF. These data suggests the presence of heterogeneous PAF receptors between the pre- and postcapillary segments of the microcirculation.

Stable VIP analogue Ro-24-9981 potentiates substance P-induced plasma exudation in hamster cheek pouch

1995 ◽  
Vol 79 (3) ◽  
pp. 968-974 ◽  
Author(s):  
X. P. Gao ◽  
H. A. Jaffe ◽  
C. O. Olopade ◽  
I. Rubinstein
Keyword(s):  
Methyl Ester ◽  
Substance P ◽  
Calcium Ionophore ◽  
Fluorescein Isothiocyanate ◽  
No Synthase ◽  
Cheek Pouch ◽  
Site Formation ◽  
Induced Responses ◽  
Hamster Cheek Pouch ◽  
Plasma Exudation

The purpose of this study was to determine whether vasoactive intestinal peptide (VIP; 300 nM) and a stable cyclic analogue of VIP, Ro-24–9981 (226 nM), modulated neurogenic plasma exudation in the oral cavity in situ and, if so, to determine the mechanisms that mediated these responses. With the use of intravital microscopy, we found that suffusion of substance P induced a significant concentration-dependent formation of fluorescein-isothiocyanate-dextran (mol wt 70 kDa) leaky sites in the hamster cheek pouch (P < 0.05). These effects were significantly and stereospecifically attenuated by NG-nitro-L-arginine methyl ester, an inhibitor of NO synthase, and restored by L-arginine, the substrate for NO synthase (P < 0.05). Topical application of human VIP and Ro-24–9981 had no significant effects of leaky site formation. In addition, human VIP had no significant effects on substance P-induced responses. By contrast, Ro-24–9981 significantly potentiated substance P- and capsaicin-induced leaky site formation (P < 0.05). The effects of Ro-24–9981 on substance P-induced responses were significantly attenuated by NG-nitro-L-arginine methyl ester and restored by L-arginine (P < 0.05). Indomethacin had no significant effects on Ro-24–9981-induced responses. Ro-24–9981 had no significant effects on adenosine- and calcium ionophore A-23187-induced leaky site formation. Collectively, these data suggest that VIP plays no significant role in modulating neurogenic plasma exudation in the oral mucosa. By contrast, Ro-24–9981 amplified this response in a specific receptor-mediated fashion.

Cigarette smoke extract potentiates bradykinin-induced increases in microvascular permeability

1993 ◽  
Vol 75 (1) ◽  
pp. 27-32 ◽  
Author(s):  
W. G. Mayhan ◽  
I. Rubinstein
Keyword(s):  
Cigarette Smoke ◽  
Fluorescein Isothiocyanate ◽  
Cigarette Smoke Extract ◽  
Microvascular Permeability ◽  
Cheek Pouch ◽  
Site Formation ◽  
Hamster Cheek Pouch ◽  
Fluorescein Isothiocyanate Dextran ◽  
Macromolecular Permeability

The first goal of this study was to determine whether cigarette smoke extract (CSE) increases microvascular permeability of the hamster cheek pouch in vivo. The second goal was to determine whether CSE potentiates bradykinin-induced increases in vascular permeability in the hamster cheek pouch. Using intravital microscopy, we examined the permeability of the hamster cheek pouch to fluorescein isothiocyanate-dextran (mol wt 70,000). Increases in permeability were quantitated by counting the number of postcapillary venular leaky sites per 0.11 cm2. Superfusion of CSE (1, 5, and 10%) did not produce venular leaky sites and, thus, did not alter macromolecular permeability. Superfusion of bradykinin (0.1, 0.5, and 1.0 microM) produced a dose-related increase in the number of venular leaky sites. Formation of leaky sites in response to bradykinin was potentiated by CSE. To determine whether potentiation of bradykinin-induced leaky site formation by CSE was related to products released via the cyclooxygenase pathway, we examined the effects of pretreatment with indomethacin (10 mg/kg i.v.). Indomethacin did not alter the potentiating effect of CSE on bradykinin-induced leaky site formation. These findings suggest that CSE does not alter basal permeability of the hamster cheek pouch microcirculation in vivo. However, CSE potentiates bradykinin-induced increases in microvascular permeability. The mechanism of CSE-induced potentiation of microvascular permeability does not appear to be related to substances produced via the cyclooxygenase pathway.

Mechanisms of T-kinin-induced increases in macromolecule extravasation in vivo

1993 ◽  
Vol 74 (6) ◽  
pp. 2896-2903 ◽  
Author(s):  
X. P. Gao ◽  
W. G. Mayhan ◽  
J. M. Conlon ◽  
S. I. Rennard ◽  
I. Rubinstein
Keyword(s):  
Mast Cells ◽  
Fluorescein Isothiocyanate ◽  
Cheek Pouch ◽  
Site Formation ◽  
Plasma Extravasation ◽  
Bradykinin Receptors ◽  
Hamster Cheek Pouch ◽  
Peripheral Microcirculation ◽  
Neurokinin 1

The purpose of this study was to investigate the mechanisms that mediate T-kinin- (Ile-Ser-bradykinin) induced increases in macromolecule extravasation in the hamster cheek pouch. Changes in plasma extravasation were quantified by counting the number of leaky sites and calculating the clearance of fluorescein isothiocyanate- (FITC) dextran (mol mass = 70 kDa) during suffusion of the cheek pouch with T-kinin (0.1–1.0 microM) by using intravital microscopy. T-kinin induced a significant time- and concentration-dependent increase in leaky site formation and clearance of FITC-dextran (P < 0.05). The increase in plasma extravasation in response to T-kinin was mediated by two mechanisms: a COOH-terminal-mediated stimulation of B2 bradykinin receptors in postcapillary venules and an NH2-terminal-mediated degranulation of mast cells leading to histamine release. Indomethacin and CP 96345, a selective nonpeptide neurokinin-1 receptor antagonist, had no significant effects on T-kinin-induced responses. We conclude that T-kinin increases macromolecule extravasation in the peripheral microcirculation by stimulating B2 bradykinin receptors in post-capillary venules and by degranulating mast cells.

scholarly journals Redundancy in the central tachykinin systems safeguards puberty onset and fertility

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.

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

1995 ◽  
Vol 268 (2) ◽  
pp. L263-L269 ◽  
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.

Platelet-activating factor stimulates protein tyrosine kinase in hamster cheek pouch microcirculation

1995 ◽  
Vol 268 (1) ◽  
pp. H399-H403 ◽  
Author(s):  
D. Kim ◽  
W. N. Duran
Keyword(s):  
Tyrosine Kinase ◽  
Protein Tyrosine Kinase ◽  
Platelet Activating Factor ◽  
Fluorescein Isothiocyanate ◽  
Cheek Pouch ◽  
Computer Assisted ◽  
Hamster Cheek Pouch ◽  
Protein Tyrosine ◽  
Macromolecular Transport ◽  
Arteriolar Tone

We studied the interactions between platelet-activating factor (PAF) and protein tyrosine kinase (PTK) in the modulation of microvascular responses in the hamster cheek pouch using intravital microscopy and computer-assisted image analysis. Changes in arteriolar diameter and in integrated optical intensity (IOI; an index of vascular permeability) were measured. Fluorescein isothiocyanate-labeled dextran 150 (FITC-Dx 150) served as a tracer for macromolecular transport. Genistein and tyrphostin 25, two PTK inhibitors, were applied topically in separate experiments. Pretreatment with 10(-4), 10(-6), and 10(-8) M genistein and with tyrphostin 25 at 10(-5) and 10(-7) M attenuated the maximal increment in mean IOI (+/- SE) induced by PAF at 10(-7) M (19.9 +/- 5.3, 21.5 +/- 4.5, 58.5 +/- 11.4, 28.7 +/- 7.6, and 35.0 +/- 10.9 vs. 70.7 +/- 8.9 units, respectively). Pretreatment with PTK inhibitors resulted in vasodilation but did not inhibit PAF-induced vasoconstriction. Our results suggest that PTK represents a biochemical pathway involved in the PAF modulation of microvascular permeability but not PAF modulation of arteriolar tone.

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