RT Journal Article
SR Electronic
T1 Ro 25-1553: a novel, long-acting vasoactive intestinal peptide agonist. Part II: Effect on in vitro and in vivo models of pulmonary anaphylaxis.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1289
OP 1294
VO 270
IS 3
A1 M O'Donnell
A1 R J Garippa
A1 N Rinaldi
A1 W M Selig
A1 J E Tocker
A1 S A Tannu
A1 M A Wasserman
A1 A Welton
A1 D R Bolin
YR 1994
UL http://jpet.aspetjournals.org/content/270/3/1289.abstract
AB Studies were conducted to compare the effect of native vasoactive intestinal peptide (VIP), Ro 25-1553 (a cyclic peptide analog of VIP) and salbutamol (a beta2-adrenoceptor agonist) on antigen-induced pathophysiological effects in the guinea pig. Ro 25-1553 and salbutamol (0.01-1.0 microM) prevented antigen-induced contractions of the guinea pig trachea in vitro with IC50 values of 0.07 and 0.05 microM, respectively. VIP (0.01-1.0 microM) had no effect on antigen-induced tracheal contractions. Aerosolized Ro 25-1553 and salbutamol were equipotent in preventing antigen-induced increases in guinea pig lung resistance (IC50 value = 0.0001%), whereas aerosolized VIP (0.1%) was ineffective. Ro 25-1553 (0.1-100 micrograms), instilled intratracheally 2 min before the antigen challenge of buffer-perfused lungs from sensitized guinea pigs, produced a dose-dependent inhibition of bronchoconstrictor, vasoconstrictor and edemagenic responses, whereas intratracheal VIP (100 micrograms) had no effect. Intratracheal salbutamol (0.1-100 micrograms) inhibited antigen-induced responses in a manner comparable to Ro 25-1553. Lung inflammation was assessed as leukocyte accumulation in bronchoalveolar lavage fluid after the antigen provocation. Aerosolized antigen-induced bronchoalveolar lavage eosinophilia (13-fold increase over saline controls) at 6 hr after challenge was prevented in a concentration-dependent manner by pretreatment with nebulized Ro 25-1553 and salbutamol, but not by pretreatment with native VIP. These results indicate that Ro 25-1553 suppresses various pathophysiological features associated with pulmonary anaphylaxis and asthma, including airway reactivity, edema formation and granulocyte accumulation.(ABSTRACT TRUNCATED AT 250 WORDS)