Stimulation by neurotensin of (3H)5-hydroxytryptamine (5HT) release from rat frontal cortex slices.
The effect of neurotensin (NT) on the K+-evoked (3H)5HT release from brain frontal cortex slices was studied in rats. NT(1-13) and NT(8-13) increased (3H)5HT release with EC50 values in the nanomolar range and Emax values in the range of 100% of control, whereas D-tyr11-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 (3H)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(-7)M, 10(-6)M) effect under K+ depolarization was drastically decreased, indicating that the NT receptor could be desensitized. No potentiating effect of NT on K+-evoked (3H)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.
Héaulme
M
M
Sanofi Recherche, Neuropsychiatry Department, Montpellier, France.
Leyris
R
R
Soubrié
P
P
Le Fur
G
G
D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D015536:Down-Regulation; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D020128:Inhibitory Concentration 50; D009496:Neurotensin / Q000031:analogs & derivatives / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D018028:Receptors, Neurotensin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D018492:Dopamine Antagonists; D007093:Imidazoles; D010446:Peptide Fragments; D011720:Pyrazoles; D011804:Quinolines; D016194:Receptors, N-Methyl-D-Aspartate; D018028:Receptors, Neurotensin; C104418:SR 142948A; C086487:SR 48527; C079087:SR 48692; D012701:Serotonin; D009496:Neurotensin; D013779:Tetrodotoxin; D016291:Dizocilpine Maleate; D000218:Adamantane; D011188:Potassium