Clinical and inflammatory responses to exogenous tachykinins in allergic rhinitis.
Our purpose was to characterize the tachykinin receptor type involved in nasal obstruction to exogenous substance P in rhinitic patients. We also attempted to assess biochemical and cellular events associated with this response. Nasal challenges were performed in seven patients with allergic rhinitis. They received increasing doses (10 to 80 nmol) of substance P, of neurokinin A, of the N-terminal fragment of substance P, substance P(1-9), and of saline on 4 different days separated by 14 days. Nasal airway resistance (NAR) increased in a dose-dependent manner on substance P. Maximal increase reached 4.5-fold basal NAR. Response to neurokinin A was significantly lower (less than 2-fold basal NAR). No effect was observed on substance P(1-9) and saline. This order of activity [substance P much greater than neurokinin A greater than substance P(1-9) = saline] indicates an NK1 receptor-mediated mechanism inducing local vasodilation. No histamine release was found after any of the four challenges. Proteins significantly increased in nasal lavage fluid on both substance P and neurokinin A, whereas substance P(1-9) and saline had no effect. The percentage of albumin increased in nasal lavage fluid from 30 to 50% of total proteins on substance P and neurokinin A, indicating microvascular leakage. Polymorphonuclear cells significantly increased from 9 to 36% on substance P, from 13 to 49% on neurokinin A, and from 13 to 55% on substance P(1-9). Eosinophils increased in five patients on substance P (from 0.1 to 5% for the group), in three patients after neurokinin A, and in two after substance P(1-9).(ABSTRACT TRUNCATED AT 250 WORDS)
Braunstein
G
G
Service de Pneumologie, UFR Cochin-Port Royal, Paris, France.
Fajac
I
I
Lacronique
J
J
Frossard
N
N
D000328:Adult; D000403:Airway Resistance; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000473:pathology; D005260:Female; D005483:Flushing / Q000175:diagnosis; D006439:Hemodynamics / Q000187:drug effects; D006632:Histamine / Q000378:metabolism; D006801:Humans; D008297:Male; D009297:Nasal Mucosa / Q000378:metabolism / Q000473:pathology; D009299:Nasal Provocation Tests; D015287:Neurokinin B / Q000494:pharmacology; D009504:Neutrophils / Q000473:pathology; D010446:Peptide Fragments; D011506:Proteins / Q000378:metabolism; D012221:Rhinitis, Allergic, Perennial / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006255:Rhinitis, Allergic, Seasonal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*
D010446:Peptide Fragments; D011506:Proteins; D015320:Tachykinins; D013373:Substance P; C035972:substance P (1-9); D006632:Histamine; D015287:Neurokinin B