Effects of neurotensin on electrical and mechanical properties of smooth muscles in longitudinal and circular layers of the guinea-pig ileum

Effects of neurotensin (NT) on the electrical and mechanical activities of longitudinal and circular muscles of the guinea-pig ileum were investigated using the micro-electrode and isometric tension recording methods. In longitudinal muscles, the resting membrane potential was not affected by NT (0.1–30 nmol/l), but NT did provoke the contraction when applied in concentrations over 1 nmol/l. TTX (0.1 mol/l) neither modified the resting membrane potential nor the contraction evoked by NT, under condition of pretreatment with - and -adrenoceptor blockers. In circular muscles, NT (over 0.1 nmol/l) consistently hyperpolarized the membrane and increased the ionic conductance. The hyperpolarization appeared with a transient hyperpolarization, which gradually declined with a long time course. Using apamin and various concentrations of Ca, the NT-induced hyperpolarization was classified into two subtypes; fast and slow. The former was composed of maximum hyperpolarization due to activations of the Ca independent K channel, and the latter was composed of late hyperpolarization, due to activations of the Ca dependent K channel. During the NT-induced hyperpolarization in circular muscles, the amplitude of non-adrenergic, noncholinergic inhibitory junction potential (i.j.p.) evoked by field stimulation was reduced. This reduction induced by 0.5 nmol/l NT was mainly due to hyperpolarization of the membrane, and that observed in a high concentration of NT (3 nmol/l) was directly involved in ionic mechanisms contributing to the generation of i.j.p. In circular muscles, NT (over 3 nmol/l) did relax the tissue pre-contracted with 17.8 mmol/l K, but NT (below 30 nmol/l) did not relax the tissue pre-contracted by 39.6 mmol/l K. The relaxation of the pre-contracted tissue induced by NT depended on the hyperpolarization induced by NT. The results indicate that NT has direct actions on muscle cells of both longitudinal and circular layers of the ileum. In longitudinal muscles, NT has no effect on the membrane potential but does produce contraction, while in circular muscles, NT activates the Ca independent and Ca dependent K channels and relaxes the tissue, by hyperpolarizing the membrane. The membrane response evoked by NT differs from that induced by the activation of non-adrenergic, non-cholinergic nerves.