Abstract
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.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Arimura A. Pituitary adenylate cyclase activating polypeptide (PACAP): discovery and current status of research. Regul Pept. 1992 Feb 18;37(3):287–303. [PubMed] [Google Scholar]
- Barnes P. J., Chung K. F., Page C. P. Inflammatory mediators and asthma. Pharmacol Rev. 1988 Mar;40(1):49–84. [PubMed] [Google Scholar]
- Barnes P. J., Dixon C. M. The effect of inhaled vasoactive intestinal peptide on bronchial reactivity to histamine in humans. Am Rev Respir Dis. 1984 Aug;130(2):162–166. doi: 10.1164/arrd.1984.130.2.162. [DOI] [PubMed] [Google Scholar]
- Bertrand C., Nadel J. A., Graf P. D., Geppetti P. Capsaicin increases airflow resistance in guinea pigs in vivo by activating both NK2 and NK1 tachykinin receptors. Am Rev Respir Dis. 1993 Oct;148(4 Pt 1):909–914. doi: 10.1164/ajrccm/148.4_Pt_1.909. [DOI] [PubMed] [Google Scholar]
- Cardell L. O., Uddman R., Luts A., Sundler F. Pituitary adenylate cyclase activating peptide (PACAP) in guinea-pig lung: distribution and dilatory effects. Regul Pept. 1991 Nov 26;36(3):379–390. doi: 10.1016/0167-0115(91)90071-n. [DOI] [PubMed] [Google Scholar]
- Dusser D. J., Umeno E., Graf P. D., Djokic T., Borson D. B., Nadel J. A. Airway neutral endopeptidase-like enzyme modulates tachykinin-induced bronchoconstriction in vivo. J Appl Physiol (1985) 1988 Dec;65(6):2585–2591. doi: 10.1152/jappl.1988.65.6.2585. [DOI] [PubMed] [Google Scholar]
- Kanemura T., Tamaoki J., Chiyotani A., Takeyama K., Sakai N., Tagaya E., Konno K. Role of Na(+)-K(+)-ATPase in airway smooth muscle relaxation by vasoactive intestinal peptide and pituitary adenylate cyclase activating peptide. Res Commun Chem Pathol Pharmacol. 1993 Jan;79(1):11–22. [PubMed] [Google Scholar]
- Luts A., Uddman R., Alm P., Basterra J., Sundler F. Peptide-containing nerve fibers in human airways: distribution and coexistence pattern. Int Arch Allergy Immunol. 1993;101(1):52–60. doi: 10.1159/000236498. [DOI] [PubMed] [Google Scholar]
- Nadel J. A. Neurogenic inflammation in airways and its modulation by peptidases. Ann N Y Acad Sci. 1992;664:408–414. doi: 10.1111/j.1749-6632.1992.tb39779.x. [DOI] [PubMed] [Google Scholar]
- O'Donnell M., Garippa R. J., Rinaldi N., Selig W. M., Tocker J. E., Tannu S. A., Wasserman M. A., Welton A., Bolin D. R. Ro 25-1553: a novel, long-acting vasoactive intestinal peptide agonist. Part II: Effect on in vitro and in vivo models of pulmonary anaphylaxis. J Pharmacol Exp Ther. 1994 Sep;270(3):1289–1294. [PubMed] [Google Scholar]
- Wallin A., Sandström T., Rosenhall L., Melander B. Time course and duration of bronchodilatation with formoterol dry powder in patients with stable asthma. Thorax. 1993 Jun;48(6):611–614. doi: 10.1136/thx.48.6.611. [DOI] [PMC free article] [PubMed] [Google Scholar]