The stable VIP analogue, Ro 24-9981, potentiates bradykinin-induced increases in clearance of macromolecules.
The purpose of this study was to determine whether the stable cyclic peptide analogue of human vasoactive intestinal peptide, Ro 24-9981, modulates bradykinin-induced plasma exudation in the oral mucosa and if so, to determine the mechanisms that mediated these responses. Using intravital microscopy, we found that suffusion of Ro 24-9981 had no significant effects on leaky site formation and clearance of fluorescein-isothiocyanate-dextran (mol mass 70 kDa) in the hamster cheek pouch. However, Ro 24-9981 significantly potentiated bradykinin-induced increases in leaky site formation and clearance of fluorescein-isothiocyanate-dextran (P < 0.05). These effects were specific because Ro 24-9981 had no significant effects on adenosine and calcium ionophore A23187-induced increases in leaky site formation and clearance of fluorescein-isothiocyanate-dextran. Furthermore, they were not mediated by cyclooxygenase products of arachidonic acid metabolism because indomethacin was ineffective. NG-nitro-L-arginine methyl ester, a selective inhibitor of nitric oxide synthase, but not NG-nitro-D-arginine methyl ester, significantly attenuated the effects of both bradykinin and Ro 24-9981 with bradykinin (P < 0.05). These responses were restored by L-arginine but not D-arginine. Collectively, these data indicate that bradykinin-induced plasma exudation in the oral mucosa was potentiated by Ro 24-9981 in a specific receptor-mediated fashion. These responses were mediated, in part, by the L-arginine/nitric oxide biosynthetic pathway.
Gao
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Department of Medicine, University of Illinois at Chicago, USA.
Rubinstein
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D000241:Adenosine / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D006224:Cricetinae; D003911:Dextrans / Q000493:pharmacokinetics*; D004357:Drug Synergism; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D046911:Macromolecular Substances; D008297:Male; D008647:Mesocricetus; D008969:Molecular Sequence Data; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010456:Peptides, Cyclic / Q000494:pharmacology*; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives* / Q000494:pharmacology
D003911:Dextrans; D046911:Macromolecular Substances; D010456:Peptides, Cyclic; C097123:Ro 24-9981; C015219:fluorescein isothiocyanate dextran; D014660:Vasoactive Intestinal Peptide; D000001:Calcimycin; D001120:Arginine; D019001:Nitric Oxide Synthase; D016650:Fluorescein-5-isothiocyanate; D000241:Adenosine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin