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Am J Physiol Heart Circ Physiol 265: H593-H598, 1993;
0363-6135/93 $5.00
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AJP - Heart and Circulatory Physiology, Vol 265, Issue 2 593-H598, Copyright © 1993 by American Physiological Society

ARTICLES

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

X. P. Gao, R. A. Robbins, R. M. Snider, J. Lowe 3rd, S. I. Rennard, P. Anding and I. Rubinstein
Department of Internal Medicine, University of Nebraska Medical Center, Omaha 68198.

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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