Biological Effects

Intravenous administration of neurotensin produces endocrine and cardiovascular effects, which include hyperglycemia, hypotension and vasodilatation.

Intracerebroventricular or intracisternal administration of neurotensin produces physiological and behavioral alterations, including potentiation of barbiturate-mediated effects and effects mediated by ethanol. In addition, it induces hypothermia, reduces food intake and prevents the development of stress-induced gastric ulcers in rats.

Furthermore, it has been demonstrated that neurotensin inhibits locomotor hyperactivity induced by dopamine agonists. Neurotensin has been shown to modulate dopaminergic transmission and to modulate dopaminergic effects in cells which possess both dopamine and neurotensin receptors. For example, the activation of neurotensin receptors located on the soma or on nerve terminals of dopaminergic neurons can facilitate dopaminergic transmission. The action of dopamine itself is to suppress dopamine release via dopaminergic autorecep-tors.

In contrast, the activation of neurotensin receptors antagonizes dopamine release at the postsynaptic level.

Neurotensin elicits hypothermic and naloxone-insensitive analgesic responses after brain injection. The effects are independent of the activation of NT-1 receptors; and recent studies (Dubuc et al. 1999) suggest that they are mediated via NT-2 receptors. An interesting point in this context is that the analgesic effect of neurotensin is not be blocked by opioid antagonists. In addition, by comparing mice deficient in the receptors NTS1 or NTS2, an involvement of NTS2 receptors in thermal nociception has been demonstrated. Thus, in a hot-plate test, a significant alteration in jump latency was observed in NTS2-deficient mice compared to NTS1-deficient or wild-type mice.

Food intake, especially the intake of lipids, induces a release of neurotensin; and increased levels of neurotensin can be detected in the circulating blood. A likely interpretation of this relationship is that neurotensin is involved in digestive processes.

Neurotensin also inhibits the secretion of gastric acid. Besides its endocrine functions, neurotensin induces paracrine effects in the periphery: these are evident as locally restricted effects on the contraction of smooth muscles in the gasto-intestinal tract and on the transepithelial transport of electrolytes.

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