NK1 receptors mediate tachykinin-induced increase in microvascular clearance in hamster cheek pouch.
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.
Gao
X P
XP
Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198.
Robbins
R A
RA
Snider
R M
RM
Lowe
J
J
Rennard
S I
SI
Anding
P
P
Rubinstein
I
I
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D002610:Cheek / Q000098:blood supply; D006224:Cricetinae; D046911:Macromolecular Substances; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000187:drug effects; D015288:Neurokinin A / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*
D001713:Biphenyl Compounds; D046911:Macromolecular Substances; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D015320:Tachykinins; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B; D002211:Capsaicin; C066892:CP 96345