Article date: July 1995
By: Anders Lindén, Shigemi Yoshihara, Brendan Chan, Jay A. Nadel, in Volume 115, Issue 6, pages 913-916
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.
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 β2‐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.
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.
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.
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.
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 β2‐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.
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.
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.
DOI: 10.1111/j.1476-5381.1995.tb15897.x
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