Pituitary adenylate cyclase-activating polypeptide, effects in the human nose.
BACKGROUND
Pituitary adenylate cyclase-activating peptide (PACAP) is a neuropeptide with strong vaso- and bronchodilator capacity. There is recent evidence that PACAP decreases the release of proinflammatory cytokines and we have previously shown that PACAP inhibits neutrophil chemotaxis in vitro, but little is known about the effects of PACAP in human upper and lower airways.


OBJECTIVE
To investigate the effects of PACAP in the human upper respiratory tract focusing on vasodilatation/nasal airway resistance (NAR), neutrophil recruitment, plasma extravasation and endogenous production of IL-1-related mediators.


METHODS
Surgical specimens from five patients (aged 19-55 years), obtained in conjunction with nasal surgery, were used for immunohistochemical localization of PACAP in the nasal mucosa. In seven, healthy, non-allergic, non-smoking subjects (aged 19-45 years), NAR was measured with rhinomanometry. Nasal lavage was performed, before and after intranasal application of PACAP (200 microL of a 1 microm PACAP solution in each nasal cavity), with and without the addition of histamine. Cells, albumin and IL-1-related mediators were analysed in nasal lavage. In addition, the effects on pulse, blood pressure, ECG and pulmonary function were evaluated.


RESULTS
In the nasal mucosa, PACAP-like immunoreactive nerve fibres were seen close to blood vessels and seromucous glands. Application of PACAP in the nasal cavity increased NAR and augmented the increase in NAR induced by histamine. In addition, PACAP inhibited histamine-induced recruitment of neutrophils, increased plasma leakage and reduced the level of IL-1RA (an endogenously produced IL-1 receptor antagonist) in nasal lavage. Cardiovascular and pulmonary parameters were not affected.


CONCLUSIONS
These results imply that PACAP is an important endogenous mediator in human upper airways, with a potential role as a regulator of vascular smooth muscle, secretion, plasma extravasation, neutrophil recruitment and cytokine activity.
Kinhult
J
J
Laboratory for Clinical and Experimental Allergy Research, Department of Otorhinolaryngology, Malmö University Hospital, Malmö, Sweden.
Adner
M
M
Uddman
R
R
Cardell
L O
LO
D000328:Adult; D000403:Airway Resistance / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D017817:Nasal Lavage Fluid / Q000166:cytology; D009297:Nasal Mucosa; D009299:Nasal Provocation Tests; D009479:Neuropeptides / Q000494:pharmacology*; D009666:Nose / Q000187:drug effects*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014665:Vasodilator Agents / Q000494:pharmacology*
C495401:ADCYAP1 protein, human; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014665:Vasodilator Agents