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Characterization of the inhibitory effect of [D-Trp11]-NT toward some biological actions of neurotensin in rats

Publication Date
DOI: 10.1016/0143-4179(83)90023-9
  • Biology
  • Pharmacology


Abstract We assessed the influence of various doses of [D-Trp 11]-NT on the increase of histaminemia and hematocrit, and decrease of blood pressure, caused by intravenous injections of neurotensin (NT), substance P (SP) and compound 48 80 ( C48 80 ) in anesthetized rats. [D-Trp 11]-NT was found to inhibit dose-dependently and selectively the changes of histaminemia, hematocrit and blood pressure caused by NT. Since the highest dose of [D-Trp 11]-NT utilized exhibited slight NT-like activity, we tested the possibility that desensitization rather than true pharmacological antagonism was responsible for the inhibitory action of [D-Trp 11]-NT toward NT. This hypothesis was verified by evaluating the influence of intravenous infusions of sub-stimulatory and slightly active doses of NT on NT-induced effects. The sub-stimulatory dose (0.1 nmoles kg −1 min −1) as well as a higher dose rate (0.2 nmole kg −1 min −1) of NT were found to inhibit markedly the changes of histaminemia, hematocrit and blood pressure evoked by bolus doses of NT, without altering the effects of C48 80 on the same parameters. These results suggest that the inhibitory action of [D-Trp 11]-NT toward NT-induced changes of histaminemia, hematocrit and blood pressure could be the result of receptor desensitization rather than to a true pharmacological antagonism. The results also suggest that the sensitivity of target tissues to exogenous NT could be modulated to some extent by endogenous circulating levels of NT.

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