Gf. Joos et al., TACHYKININS CONTRACT TRACHEA FROM FISCHER-344 RATS BY INTERACTION WITH A TACHYKININ NK1 RECEPTOR, European journal of pharmacology, 271(1), 1994, pp. 47-54
The contractile effect of substance P, neurokinin A, carbachol and ser
otonin (5-HT) on isolated Fischer 344 rat trachea was studied. Contrac
tions of two distal tracheal rings were measured isometrically in a 2-
ml organ bath. Cumulative concentration-response curves were obtained
for carbachol (EC(50) ring 1: 1.6 X 10(-7) M and ring 2: 2.2 x 10(-7)
M) and for 5-HT (EC(50) 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 EC(50)(X 10(-7) M) of 1.10+/-0.27 and 1.97+/-0.45 respectively. Th
e maximal contraction was 32.6+/-2.5% (substance P) and 32.6+/-1.5% (n
eurokinin A) of the maximal contraction with carbachol. In contrast, n
either substance P nor neurokinin A caused contraction of trachea from
BDE rats. The tachykinin NK2 receptor agonist, Ac[Arg(6),Sar(9),Met(O
-2)(11)]substance P-(6-11), caused a concentration-dependent contracti
on with an EC(50)(X 10(-9) M) of 1.38+/-0.09 and a maximal effect of 2
5.5+/-2.1% of the maximal contraction with carbachol. The tachykinin N
K2 receptor agonist, [beta-Ala(8)]neurokinin A-(4-10), had a small con
tractile effect at 10(-6) M (8.4+/-0.8% of the maximal contraction wit
h carbachol) while the tachykinin NK3 receptor agonist, senktide, had
no effect up to 3.3 x 10(-6) M. The tachykinin NK1 receptor antagonist
, (+/-)-RP67580 (7,7-diphenyl-2-(1-imino-2-(2-methoxyphenylethyl)- per
hydraisoinotol-4-one))) (3 X 10(-9) to 10(-7) M), produced a concentra
tion-dependent rightward shift of the concentration-response curve for
neurokinin A (Schild plot: slope 1.13, x-intercept 8.4). The tachykin
in NK2 receptor antagonist, SR48968 ((S)-N-methyl-N[4-(4-acetylamine-4
-phenyl- piperidino)-2-(3,4-dichlorophenyl) butylbenzamide) (10(-8) to
10(-6) M), had no major effect on the concentration-response for neur
okinin A. We conclude that substance P and neurokinin A contract Fisch
er 344 rat trachea mainly by interaction with a tachykinin NK1 recepto
r.