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 (RL) 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 RL caused by inhaled ovalbumin and histamine. At the highest dose, PACAP 1-27 prevented the increase in RL 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 RL 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 RL 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.
Lindén
A
A
Cardiovascular Research Institute, University of California, San Francisco 94143-0130, USA.
Yoshihara
S
S
Chan
B
B
Nadel
J A
JA
D000262:Adenylyl Cyclases / Q000187:drug effects*; D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D010047:Ovalbumin / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D010902:Pituitary Gland / Q000187:drug effects*; D011652:Pulmonary Circulation / Q000187:drug effects; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
D001993:Bronchodilator Agents; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014665:Vasodilator Agents; D006632:Histamine; D010047:Ovalbumin; D000262:Adenylyl Cyclases