INHIBITION OF BRONCHOCONSTRICTION BY PITUITARY ADENYLATE-CYCLASE ACTIVATING POLYPEPTIDE (PACAP-1-27) IN GUINEA-PIGS IN-VIVO

1 We studied the inhibitory effect of pituitary adenylate cyclase activating polypeptide (PACAP 1-27) on the increase in total pulmonary resistance (R(L)) caused either by allergen or histamine in anaesthetized, ventilated guinea-pigs. 2 PACAP 1-27 given via i.v. infusion (0.045-4.5 nmol kg(-1) min(-1)) dose-dependently reduced the increase in R(L) caused by inhaled ovalbumin and histamine. At the highest dose, PACAP 1-27 prevented the increase in R(L) caused by ovalbumin and histamine completely. Infusion of PACAP 1-27 and the beta(2)-adrenoceptor agonist, salbutamol (0.045-4.5 nmol kg(-1) min(-1)) inhibited the increase in R(L) similarly, but salbutamol increased the heart rate more than PACAP 1-27. 3 PACAP 1-27 and salbutamol given via inhaled aerosol (0.1 mM, 20 breaths) significantly reduced the increase in R(L) caused by histamine infused i.v., whereas aerosolised sterile saline did not. Both PACAP 1-27 and salbutamol caused bronchodilator effects within 1 min of drug inhalation and these effects remained throughout the 20 min of study. 4 Because PACAP 1-27 produced significant bronchodilatation and rapid onset of sustained action in vivo and without pronounced cardiovascular side effects, we conclude that this peptide may have therapeutic potential as a bronchodilator.