Pulmonary actions of the neurokinin1-specific agonist [Sar9,Met(O2)11]-substance P.
We examined the relationship between airway obstruction and plasma extravasation produced by the intravenous administration of the selective NK1 receptor agonist [Sar9, Met(O2)11]-substance P(SP). Conscious guinea-pigs were injected with Evans' blue dye followed by intravenous [Sar9,Met(O2)11]-SP. Animals were killed 3 min later and airway obstruction, determined via excised lung gas volumes, and plasma extravasation in the trachea, mainstem bronchi and intrapulmonary airways quantitated. Maximal plasma protein extravasation occurred at a dose about 30 times less than that required to elicit airway obstruction. Neither the neutral endopeptidase (NEP) inhibitor, thiorphan, or the angiotensin-converting enzyme (ACE) inhibitor, captopril, altered the extravasation response to [Sar9,Met(O2)11]-SP. However, thiorphan alone or combined with captopril produced a small but significant potentiation of the airway obstructive response. The marked difference between pulmonary gas trapping and Evans' blue extravasation responses suggest that [Sar9,Met(O2)11]-SP-induced airway obstruction is not secondary to increased pulmonary edema.
Yiamouyiannis
C A
CA
Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Stengel
P W
PW
Cockerham
S L
SL
Silbaugh
S A
SA
D000818:Animals; D001980:Bronchi; D004305:Dose-Response Relationship, Drug; D005070:Evans Blue; D005119:Extravasation of Diagnostic and Therapeutic Materials; D006168:Guinea Pigs; D008297:Male; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D012123:Pulmonary Ventilation; D018040:Receptors, Neurokinin-1 / Q000819:agonists*; D012137:Respiratory System / Q000187:drug effects*; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology; D014132:Trachea
D018040:Receptors, Neurokinin-1; C062618:substance P, Sar(9)-Met(O2)(11)-; D013373:Substance P; D005070:Evans Blue