title: Pituitary adenylate cyclase-activating peptide 38 a potent endogenously produced dilator of human airways.
abstract: Pituitary adenylate cyclase-activating peptide (PACAP) 38 displays several biological activities relevant to obstructive airway disease. In this study, the occurrence of PACAP 38 in human small bronchi and corresponding pulmonary arteries was analysed immunocytochemically. The dilatory effects of this peptide on the same structures were also studied in vitro. A moderate number of PACAP-like immunoreactive nerve fibres was seen in association with bronchial and vascular smooth muscle and around seromucous glands. PACAP 38 caused a concentration-dependent relaxation of precontracted bronchial and pulmonary arterial segments. The maximal relaxation was more pronounced in the airways than in the arteries, whereas the potency in both was identical. PACAP 38 caused relaxation of all segments tested (nine patients), whereas vasoactive intestinal polypeptide (VIP) failed to cause relaxation of bronchial segments from six of nine patients. Both PACAP and VIP dilated all pulmonary arterial segments tested. In conclusion, pituitary adenylate cyclase-activating peptide 38 is a potent dilator of human bronchi and is present in the human lung. Pituitary adenylate cyclase-activating peptide 38 may, therefore, play a role in the endogenous regulation of airway tone. The inhibitory effects of pituitary adenylate cyclase-activating peptide 38 are more consistent than those of the related neuropeptide vasoactive intestinal polypeptide, perhaps reflecting a difference in susceptibility to degrading enzymes.
authors.affiliation: Dept of Otorhinolaryngology, Malmö General Hospital, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Kinhult
authors.forename: J A
authors.initials: JA
authors.lastname: Andersson
authors.forename: R
authors.initials: R
authors.lastname: Uddman
authors.forename: P
authors.initials: P
authors.lastname: Stjärne
authors.forename: L O
authors.initials: LO
authors.lastname: Cardell
mesh_terms: D000368:Aged; D001980:Bronchi / Q000294:innervation / Q000378:metabolism; D001993:Bronchodilator Agents / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D009412:Nerve Fibers / Q000737:chemistry; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011651:Pulmonary Artery / Q000294:innervation / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
chemical_list: C495401:ADCYAP1 protein, human; D001993:Bronchodilator Agents; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014660:Vasoactive Intestinal Peptide