Tachykinin-induced nasal fluid secretion and plasma exudation in the rat: effects of peptidase inhibition.
Substance P (SP) evokes fluid secretion and plasma extravasation when applied to the nasal mucosa of rats. SP and another tachykinin, neurokinin A (NKA), are degraded in vitro by neutral endopeptidase (NEP) and angiotensin-1-converting enzyme (ACE). In this study, NKA or SP were applied locally to the nasal mucosa of rats. Subsequent fluid secretion was measured by a filter paper technique. Plasma exudation was derived as the recovery of intravenous (i.v.) administered 125I-albumin from the fluid-containing filter papers. In order to inhibit enzymatic degradation of the tachykinins by NEP and ACE, the rats were treated with i.v. administered phosphoramidon or captopril respectively or their combination. SP evoked fluid secretion that was augmented by phosphoramidon and further enhanced by adding captopril. NKA evoked nasal fluid secretion less effectively than SP and the effect was unaffected by peptidase inhibition. SP, but not NKA, evoked increased plasma exudation but only after pre-treatment with phosphoramidon.
Lindell
E
E
Department of Otorhinolaryngology, General Hospital, Malmö, Sweden.
Svensjö
M E
ME
Malm
L
L
Petersson
G
G
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006020:Glycopeptides / Q000494:pharmacology; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects / Q000378:metabolism*; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000378:metabolism; D015288:Neurokinin A / Q000494:pharmacology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D006020:Glycopeptides; D011480:Protease Inhibitors; D015320:Tachykinins; D013373:Substance P; D015288:Neurokinin A; D002216:Captopril; D007703:Peptidyl-Dipeptidase A; D015260:Neprilysin; C008890:phosphoramidon