Tachykinins contract trachea from Fischer 344 rats by interaction with a tachykinin NK1 receptor.
The contractile effect of substance P, neurokinin A, carbachol and serotonin (5-HT) on isolated Fischer 344 rat trachea was studied. Contractions of two distal tracheal rings were measured isometrically in a 2-ml organ bath. Cumulative concentration-response curves were obtained for carbachol (EC50 ring 1: 1.6 x 10(-7) M and ring 2: 2.2 x 10(-7) M) and for 5-HT (EC50 ring 1: 10.2 x 10(-7) M and ring 2: 10.5 x 10(-7) M). Non-cumulative administration of substance P and neurokinin A (10(-8) to 10(-5) M) caused a concentration-dependent contraction with an EC50 (x 10(-7) M) of 1.10 +/- 0.27 and 1.97 +/- 0.45 respectively. The maximal contraction was 32.6 +/- 2.5% (substance P) and 32.6 +/- 1.5% (neurokinin A) of the maximal contraction with carbachol. In contrast, neither substance P nor neurokinin A caused contraction of trachea from BDE rats. The tachykinin NK1 receptor agonist, Ac[Arg6, Sar9, Met(O2)11] substance P-(6-11), caused a concentration-dependent contraction with an EC50 (x 10-(-9) M) of 1.38 +/- 0.09 and a maximal effect of 25.5 +/- 2.1% of the maximal contraction with carbachol. The tachykinin NK2 receptor agonist, [beta-Ala8]neurokinin A-(4-10), had a small contractile effect at 10(-6) M (8.4 +/- 0.8% of the maximal contraction with carbachol) while the tachykinin NK3 receptor agonist, senktide, had no effect up to 3.3 x 10(-6) M.(ABSTRACT TRUNCATED AT 250 WORDS)
Joos
G F
GF
Department of Respiratory Diseases, University of Ghent Medical School, Belgium.
Lefebvre
R A
RA
Kips
J C
JC
Pauwels
R A
RA
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D015288:Neurokinin A / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D051381:Rats; D011916:Rats, Inbred F344; D018040:Receptors, Neurokinin-1 / Q000819:agonists*; D018041:Receptors, Neurokinin-2 / Q000819:agonists / Q000037:antagonists & inhibitors; D018042:Receptors, Neurokinin-3 / Q000819:agonists / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects*
D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D015320:Tachykinins; D012701:Serotonin; D013373:Substance P; D015288:Neurokinin A; D002217:Carbachol