Ca. Maggi et al., NITRIC-OXIDE IS THE MEDIATOR OF TACHYKININ-NK(3) RECEPTOR-INDUCED RELAXATION IN THE CIRCULAR MUSCLE OF THE GUINEA-PIG ILEUM, European journal of pharmacology, 240(1), 1993, pp. 45-50
The tachykinin NK3 receptor agonist, senktide, produces concentration-
dependent contraction of the circular muscle of the guinea-pig ileum (
EC50 2.59 nM). In the presence of the blocker of neuronal type of volt
age-sensitive calcium channels, omega-conotoxin (0.1 muM), the contrac
tile response to allow concentration of senktide was converted to an i
nhibitory effect on spontaneous activity of the ileum. This inhibitory
effect was further enhanced in the presence of atropine (1 muM) and w
as abolished by tetrodotoxin (1 muM), indicating its neural origin. In
the presence of atropine and omega-conotoxin, the inhibitory response
to senktide (1 nM) was greatly inhibited or even abolished by L-nitro
arginine (30 muM), its effect being prevented by L-arginine but not by
D-arginine (300 muM in each case). Apamin (0.1 muM) failed to signifi
cantly affect the inhibitory response to senktide. Apamin enhanced spo
ntaneous activity of the preparation while L-nitroarginine had no effe
ct. Neither apamin nor L-nitroarginine affected the inhibitory respons
e to isoprenaline. These findings indicate that inhibition of circular
muscle activity produced through NK3 receptor stimulation in the guin
ea-pig ileum is mediated through a neuronal pathway involving nitric o
xide or a nitric oxide-like substance(s) generation.