INVOLVEMENT OF POTENTIALLY DISTINCT NEUROTENSIN RECEPTORS IN NEUROTENSIN-INDUCED STIMULATION OF STRIATAL [H-3] DOPAMINE RELEASE EVOKED BY KCL VERSUS ELECTRICAL DEPOLARIZATION

We intended to determine whether the effect of neurotensin (NT) on Kand electrically evoked [H-3]dopamine (DA) release from rat and guinea -pig striatal slices involved different mechanisms and/or receptors. I n the two species, NT and three NT agonists were found to exhibit diff erent relative potencies to enhance K+-and electrically-evoked [H-3]DA release. NT(1-13) increased [H-3]DA release with EC50 values in the n anomolar range and E-max values in the range of 100% of control. NT(8- 13) and Eisai hexapeptide were both as active as NT(1-13) under K+ dep olarization, but did not exceed 40% of the NT(1-13) effect under elect rical depolarization. In rats, when [H-3]DA release was stimulated wit h two successive K+ depolarizations, in the presence of NT(1-13), the NT effect during the second exposure to K+ was drastically decreased, suggesting that the NT receptor was desensitized. The desensitization process was essentially observed on E-max values, EC50 values being we akly affected. Similar results were obtained in guinea pig. In contras t, with two electrical depolarizations or with two different depolariz ations (K+ followed by electrical), the NT effect during the second de polarization was not significantly affected. Concerning NT antagonists , SR 48692 antagonized with IC50 values in the nanomolar range the NT( 1-13) stimulated K+-evoked [H-3]DA release but did not affect, up to 1 0(-6) M, the NT(1-13) enhancement of electrically stimulated [H-3]DA r elease. On the contrary, SR 142948A antagonized the NT(1-13) effect on K+-and electrically-evoked [H-3]DA release. In conclusion, these resu lts suggest the possible existence of potentially distinct neurotensin receptors differentially involved in the control exerted by NT on DA release under KCI vs electrical depolarization. (C) 1997 Elsevier Scie nce Ltd.