Effects of selective tachykinin-receptor antagonists on tachykinin-induced airway mucus secretion in the rat.
Tachykinins like substance P (SP), neurokinin A (NKA), neurokinin B (NKB) differentially stimulate airway mucus secretion with the following rank order of potency in rat trachea: SP>NKA>NKB. These differential actions are most likely due to different affinities to the tachykinin receptors, termed neurokinin (NK)(1), NK(2)and NK(3). In this study we characterized the receptor subtype responsible for the differential secretagogue effects in rat trachea by means of selective receptor antagonists and receptor agonists.SR 140333 [NK(1)-antagonist] completely inhibited SP action (283,29+/-21, 12%-->84,53+/-4, 09%; P<0,01) and significantly reduced the effects of NKA (179,08+/-17,34%-->118,86+/-6,7%; P<0,01) and NKB (171,89+/-5, 75%-->109,5+/-4,11%; P<0,01). SR 48968 [NK(2)-antagonist] did not affect SP action, but reduced the effects of NKA and NKB. SR 142801 [NK(3)-antagonist] did not change any effect of SP, NKA or NKB. [Sar(9)]SP (NK(1)-agonist) caused strong dose-dependent secretagogue effects similar to SP, [betaAla(8)]NKA (NK(2)-agonist) showed only slight and [Pro(7)]NKB (NK(3)-agonist) no effects. The present data suggest that the secretagogue effects elicited by tachykinins in rat trachea are mediated via NK(1)receptors.
Wagner
U
U
Department of Internal Medicine, Philipps-University, Marburg/Lahn, Germany. wagnerul@mailer.uni-marburg.de
Fehmann
H
H
Bredenbröker
D
D
Klüber
D
D
Lange
A
A
Wichert
P
P
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D008297:Male; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D015287:Neurokinin B / Q000031:analogs & derivatives / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000819:agonists; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000037:antagonists & inhibitors; D018042:Receptors, Neurokinin-3 / Q000819:agonists / Q000037:antagonists & inhibitors; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*; D020545:Respiratory Mucosa / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*; D014132:Trachea / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*
D001549:Benzamides; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D018039:Receptors, Tachykinin; D015320:Tachykinins; C085215:SR 140333; D013373:Substance P; C073839:SR 48968; D015288:Neurokinin A; D015287:Neurokinin B; C091554:SR 142801