Corticotropin-releasing factor inhibits antigen-induced plasma extravasation in airways.
We investigated the potential of corticotropin-releasing factor (CRF) to reduce neurogenic plasma extravasation in sensitised guinea pig airways evoked by antigen challenge. Inhalation of 5% ovalbumin for 2 min in the presence of phosphoramidon (2.5 mg/kg, i.v.) increased extravasation of Evans blue dye in the trachea and main bronchi. The increase in plasma extravasation induced by antigen challenge was significantly reduced by pretreatment with CRF (30 nmol/kg, i.v.) (73% in the trachea and 42% in the main bronchi). The inhibition of plasma extravasation by CRF (30 nmol/kg, i.v.) alone was not different from the inhibition induced by the combination of CRF and the tachykinin NK1 receptor antagonist, CP-99,994 (4 mg/kg, i.v.) (73% in the trachea and 38% in the main bronchi). CRF (30 nmol/kg, i.v.) inhibited by 32% in the trachea and by 43% in the main bronchi plasma extravasation induced by aerosolised bradykinin but did not reduce the plasma extravasation caused by aerosolised substance P in the presence of phosphoramidon. These findings suggest that CRF reduces ovalbumin-induced plasma extravasation in guinea pig airways by inhibiting the release of tachykinins from primary sensory nerves.
Yoshihara
S
S
Cardiovascular Research Institute, University of California San Francisco 94143, USA.
Ricciardolo
F L
FL
Geppetti
P
P
Lindén
A
A
Hara
M
M
Chan
B
B
Nadel
J A
JA
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D006020:Glycopeptides / Q000494:pharmacology; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000378:metabolism
D006020:Glycopeptides; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011480:Protease Inhibitors; D015320:Tachykinins; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D013373:Substance P; D003346:Corticotropin-Releasing Hormone; C008890:phosphoramidon