Eur Respir J 1999; 14: 443-451
Copyright © ERS Journals Ltd 1999
Bronchodilation by pituitary adenylate cyclase-activating peptide and related peptides
A Linden,
LO Cardell,
S Yoshihara,
and
JA Nadel
Pituitary adenylate cyclase-activating peptide (PACAP) is present in nerves in the vicinity of bronchial and vascular smooth muscle in the airways. At least one endogenous form of PACAP, PACAP 1-27, has high affinity binding sites in the lung, probably including cholinergic nerve terminals, bronchial smooth muscle, epithelial and mononuclear inflammatory cells. The mechanism of action for PACAP 1-27 and 1-38 in vivo involves endogenous catecholamines, peptidases and nitric oxide, depending on tissue type. Intracellularly, cyclic adenosine monophosphate (cAMP) as well as calcium and sodium mobilization is probably involved. PACAP 1-27 and 1-38 inhibit airway smooth muscle tone in vitro and in vivo. The inhibitory effect of PACAP 1-38 is more sustained than that of PACAP 1-27, in vitro as well as in vivo. PACAP 1-38 also causes more sustained inhibition of bronchoconstriction after inhalation in vivo, than does vasoactive intestinal peptide (VIP). PACAP 1-27 given intravenously virtually abolishes allergen-induced bronchoconstriction in vivo. Novel synthetic analogues of PACAP 1-27 cause more sustained inhibition of airway smooth muscle tone in vitro and in vivo than do PACAP 1-27 or 1-38. Both PACAP 1-27 and 1-38 inhibit arterial smooth muscle tone but, administration of PACAP 1-27, 1-38 or a structural analogue of PACAP 1-27 in the airways, induces no cardiovascular side effects at doses inhibiting bronchoconstriction. PACAP 1-38 enhances phagocytosis in macrophages and inhibits the release of the pro-inflammatory cytokine interleukin-2 in lymphocytes, suggesting antiinflammatory effects. It is concluded that pituitary adenylate cyclase-activating peptide 1-27 and 1-38, or structurally related molecules, may be useful as bronchodilators but their effect on human bronchial smooth muscle and on human inflammatory cells is in need of evaluation.
This article has been cited by other articles:

|
 |

|
 |
 
D. Vaudry, A. Falluel-Morel, S. Bourgault, M. Basille, D. Burel, O. Wurtz, A. Fournier, B. K. C. Chow, H. Hashimoto, L. Galas, et al.
Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery
Pharmacol. Rev.,
September 1, 2009;
61(3):
283 - 357.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S-B. Catrina and L. Juntti-Berggren
Breathless after separation... from tumour
Eur. Respir. J.,
November 1, 2008;
32(5):
1420 - 1421.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. H. Sze, H. Zhou, Y. Yang, M. He, Y. Jiang, and A. O. L. Wong
Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) as a Growth Hormone (GH)-Releasing Factor in Grass Carp: II. Solution Structure of a Brain-Specific PACAP by Nuclear Magnetic Resonance Spectroscopy and Functional Studies on GH Release and Gene Expression
Endocrinology,
October 1, 2007;
148(10):
5042 - 5059.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. J. Canning
Reflex regulation of airway smooth muscle tone
J Appl Physiol,
September 1, 2006;
101(3):
971 - 985.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. M. Braas, V. May, P. Zvara, B. Nausch, J. Kliment, J. D. Dunleavy, M. T. Nelson, and M. A. Vizzard
Role for pituitary adenylate cyclase activating polypeptide in cystitis-induced plasticity of micturition reflexes
Am J Physiol Regulatory Integrative Comp Physiol,
April 1, 2006;
290(4):
R951 - R962.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Otto, L. Hein, M. Brede, R. Jahns, S. Engelhardt, H.-J. Grone, and G. Schutz
Pulmonary Hypertension and Right Heart Failure in Pituitary Adenylate Cyclase-Activating Polypeptide Type I Receptor-Deficient Mice
Circulation,
November 16, 2004;
110(20):
3245 - 3251.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Vaudry, B. J. Gonzalez, M. Basille, L. Yon, A. Fournier, and H. Vaudry
Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: From Structure to Functions
Pharmacol. Rev.,
June 1, 2000;
52(2):
269 - 324.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 1999 by the European Respiratory Society.
|