Substance P as neurogenic mediator of antidromic vasodilation and neurogenic plasma extravasation

1979 ◽  
Vol 310 (2) ◽  
pp. 175-183 ◽  
Author(s):  
Fred Lembeck ◽  
Peter Holzer
Keyword(s):  
Substance P ◽  
Plasma Extravasation ◽  
Antidromic Vasodilation ◽  
Neurogenic Plasma Extravasation

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.

Sequence of events in substance P-mediated plasma extravasation in rat skin

1989 ◽  
Vol 500 (1-2) ◽  
pp. 256-262 ◽  
Author(s):  
Zeinab Khalil ◽  
Robert D. Helme
Keyword(s):  
Substance P ◽  
Plasma Extravasation ◽  
Rat Skin ◽  
Sequence Of Events

Plasma extravasation induced by neurokinins in conscious rats: receptor characterization with agonists and antagonists

1993 ◽  
Vol 71 (3-4) ◽  
pp. 217-221 ◽  
Author(s):  
Mauro Nicolau ◽  
Martin G. Sirois ◽  
Michel Bui ◽  
Gérard E. Plante ◽  
Pierre Sirois ◽  
...  
Keyword(s):  
Substance P ◽  
Urinary Bladder ◽  
Vascular Permeability ◽  
Blue Dye ◽  
Receptor Subtype ◽  
Plasma Extravasation ◽  
Functional Sites ◽  
Conscious Rats ◽  
Selective Antagonists ◽  
Selective Agonists

The purpose of the present experiments was to study the effects of various neurokinin related peptides, such as substance P, [βAla8]NKA(4–10), and [MePhe7]NKB, which are selective for NK-1, NK-2, and NK-3 functional sites, respectively, to induce plasma extravasation in rats and the effectiveness of RP 67580 and CP-96,345 (two nonpeptide NK-1 receptor selective antagonists) and SR 48968 (a nonpeptide NK-2 receptor selective antagonist) to prevent such an effect. Bolus intravenous injection of substance P (1.0 nmol/kg) into conscious rats induced extravasation of Evans blue dye (EB), a selective marker of albumin vascular permeability, in the duodenum, the stomach, the pancreas, and the urinary bladder by 50, 40, 58, and 312%, respectively; a slight increment occurred also in the ileum and the kidney but was not significant. [βAla8]NKA(4–10) (1.0 nmol/kg) increased EB extravasation in the stomach and the urinary bladder by 52 and 99%, respectively, while [MePhe7]NKB (1.0 nmol/kg) did the same in the stomach, the ileum, and the urinary bladder by 58, 50, and 79%. Pretreatment with RP 67580 (250 nmol/kg) blocked the albumin extravasation mediated by substance P in the duodenum, the pancreas, and the urinary bladder by 100, 100, and 78%, respectively. CP-96,345 (250 nmol/kg) also inhibited EB extravasation mediated by substance P in the duodenum and the pancreas by 100 and 100%, respectively, but was ineffective in the urinary bladder. Neither RP 67580 nor CP-96,345 prevented the substance P mediated extravasation in the stomach. RP 67580 and CP-96,345 did not antagonize the effects of NK-2 and NK-3 selective agonists. SR 48968 (500 nmol/kg) was inactive against substance P as well as against the NK-2 or NK-3 selective agonists. RP 67580 (250 nmol/kg), CP-96,345 (250 nmol/kg), and SR 48968 (500 nmol/kg) per se did not induce any plasma extravasation, except in the urinary bladder, where CP-96,345 and SR 48968 increased EB concentrations in the tissue. These results suggest that the effects of neurokinins on vascular permeability vary from one tissue to another. The blockade of substance P by the NK-1 receptor selective antagonists, RP 67580 and CP-96,345, suggests that NK-1 receptors play an important role in the plasma extravasation induced by substance P. However, the effects of NK-2 and NK-3 receptor selective agonists appear to be independent of activation of NK-1 receptors since they are not blocked by RP 67580 or CP-96,345. Furthermore, because the effect of [βAla8]NKA(4–10), the NK-2 selective agonist, was not abolished by SR 48968, it is suggested that it might be mediated by the NK-2 receptor subtype NK-2B, which is less sensitive to SR 48968 than is NK-2A. The contribution of NK-3 receptors to plasma extravasation could not be adequately demonstrated in the present study because NK-3 antagonists sufficiently active in vivo are not available.Key words: neurokinins, RP 67580, CP-96,345, SR 48968, vascular permeability.

VIP modulates substance P-induced plasma extravasation in vivo

1988 ◽  
Vol 151 (2) ◽  
pp. 281-287 ◽  
Author(s):  
Zeinab Khalil ◽  
Paul V. Andrews ◽  
Robert D. Helme
Keyword(s):  
Substance P ◽  
Plasma Extravasation
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