NITRIC-OXIDE IS THE MEDIATOR OF TACHYKININ-NK(3) RECEPTOR-INDUCED RELAXATION IN THE CIRCULAR MUSCLE OF THE GUINEA-PIG ILEUM

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.