Tachykinin receptors involved in the contractile effect of the natural tachykinins in the rat gastric fundus.
1. The receptors involved in mammalian tachykinin-induced contractions of longitudinal smooth muscle strips of the rat gastric fundus were characterized pharmacologically. 2. Substance P (SP), neurokinin A, neurokinin B and senktide contracted the strips in a concentration-dependent manner with a potency order of neurokinin A > or = senktide > neurokinin B > substance P. The contractions were not influenced by tetrodotoxin and atropine. 3. L 659877, a NK2B-receptor-preferring antagonist reduced neurokinin A- and neurokinin B-induced contractions (estimated pKB 6.9 and 6.3, respectively) but had less pronounced effects on SP-induced contractions and none on contractions induced by senktide. MEN 10376, an NK2A-receptor-preferring antagonist, reduced the neurokinin A-induced contractions (estimated pKB 5.2), while dactinomycin, reduced the neurokinin A-induced contractions only to a minor extent at 10(-4) M. 4. CP 96345, an NK 1-receptor antagonist, reduced substance P- and neurokinin A-induced responses, but also reduced the contractions induced by KCl and methacholine. RP 67580, another non-peptide NK1-receptor antagonist had no effect on the substance P-, neurokinin A- and neurokinin B-induced contractions up to a concentration of 3 x 10(-6) M. 5. These results suggest that the mammalian tachykinins induce contractions of the longitudinal smooth muscle strip of the rat gastric fundus by direct action at muscular NK2B- and NK3-receptors.
Smits
G J
GJ
Heymans Institute of Pharmacology, University of Gent Medical School, Belgium.
Lefebvre
R A
RA
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005748:Gastric Fundus / Q000187:drug effects* / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D016210:Methacholine Chloride / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D015287:Neurokinin B / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D018039:Receptors, Tachykinin / Q000187:drug effects* / Q000502:physiology; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D015320:Tachykinins / Q000502:physiology*
D001713:Biphenyl Compounds; D007211:Indoles; D054833:Isoindoles; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D018039:Receptors, Tachykinin; D015320:Tachykinins; D016210:Methacholine Chloride; C054724:senktide; C073361:cyclo(Gln-Trp-Phe-Gly-Leu-Met); C069192:neurokinin A(4-10), Tyr(5)-Trp(6,8,9)-Lys(10)-; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B; C066892:CP 96345