Stimulation by neurotensin of (3H)5-hydroxytryptamine (5HT) release from rat frontal cortex slices

The effect of neurotensin (NT) on the K+-evoked (H-3)5HT release from brain frontal cortex slices was studied in rats. NT(1-13) and NT(8-13) increased (H-3)5HT release with EC50 values in the nanomolar range and Emax values in the range of 100% of control, whereas D-tyr(11)-NT was inactive. Concerning NT receptor antagonists, SR 48692 and SR 142948A antagonized with IC50 values of 4.8 +/- 1.8 nM and 4.5 +/- 1.8 nM respectively, the NT stimulated K+-evoked (3H)5HT release. SR 48527 also antagonized NT induced (H-3)5HT release with an IC50 value of 0.95 +/- 0.06 nM whereas the inactive R(-) enantiomer SR 49711 only inhibited this effect with IC50 value close to 10(-6)M. The 5HT-releasing effect of NT was completely inhibited by tetrodotoxin suggesting that NT receptors involved in the control of 5-HT release are not located on 5-HT terminals. After a first NT (10(-7)M) application, the NT (10-7M, 10-6M) effect under K+ depolarization was drastically decreased, indicating that the NT receptor could be desensitized. No potentiating effect of NT on K+-evoked (H-3)5HT release was observed in striatal and hippocampal slices. These results suggest that, in the rat frontal cortex, NT regulates 5HT release through a high affinity NT receptor not associated with 5HT terminals.