Pharmacological characterization of the inhibitory effects of neurotensin on the rabbit ileum myenteric plexus preparation

1 Neurotensin in picomolar concentrations caused a concentration-related inhibition of the spontaneous contractile activity of the longitudinal muscle from the rabbit isolated ileum. Neurotensin was approximately 100 times more potent than adrenaline and about 10000 times as active as adenosine triphosphate (ATP) in producing similar relaxations. 2 The neurotensin-induced inhibitory effect did not follow activation of adrenoceptors or P1-purinoceptors since the effect of the neuropeptide was not antagonized by a combination of phentolamine plus (−)-propranolol, nor by pretreatment with theophylline. 3 Tetrodotoxin did not reduce the potency of neurotensin in relaxing the rabbit ileum, suggesting that the neurotensin-induced inhibition is not neuronally mediated. The inhibitory responses of neurotensin were blocked non-competitively by apamin. 4 The inhibitory effect of neurotensin was short-lived with the subsequent development of tachyphylaxis, which was not crossed to the inhibitory action of adrenaline or ATP. Similarly, when tachyphylaxis to adrenaline or to ATP was established, the inhibitory action of neurotensin was unaffected. Desensitization was characterized by a gradual shift of the neuropeptide concentration-response curve to the right and downwards. 5 Preincubation of rabbit ileum strips with 10 nm dynorphin (1–13) significantly increased the inhibitory action of neurotensin.