The stable vip analog, ro 24-9981, potentiates substance p-induced plasma exudation in the hamster cheek pouch. Gao, Xiao-Pei, H. Ari Jaffe, Christopher O. Olopade, and Israel Rubinstein. Department of Medicine, University of Illinois at Chicago College of Medicine, and West Side Department of Veterans Affairs Medical Center, Chicago, Illinois 60612-7323
APStracts 2:0192A, 1995.
The purpose of this study was to determine whether vasoactive intestinal peptide (VIP; 300 nM) and a stable cyclic analog 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. Using intravital microscopy, we found that suffusion of substance P induced a significant, concentration -dependent formation of fluorescein-isothiocyanate (FITC)-dextran (m.w.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 (L-NAME), an inhibitor of nitric oxide (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 L-NAME 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 A23187-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. 

Received 19 May 1994; accepted in final form 27 April 1995.
APS Manuscript Number A469-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on  9 May 1995.