Involvement of potentially distinct neurotensin receptors in neurotensin-induced stimulation of striatal [3H]dopamine release evoked by KCl versus electrical depolarization
Abstract
We intended to determine whether the effect of neurotensin (NT) on K+ and electrically evoked [3H]dopamine (DA) release from rat and guinea-pig striatal slices involved different mechanisms and/or receptors. In the two species, NT and three NT agonists were found to exhibit different relative potencies to enhance K+- and electrically-evoked [3H]DA release. NT(1-13) increased [3H]DA release with EC50 values in the nanomolar range and Emax values in the range of 100% of control. NT(8-13) and Eisai hexapeptide were both as active as NT(1-13) under K+ depolarization, but did not exceed 40% of the NT(1-13) effect under electrical depolarization. In rats, when [3H]DA release was stimulated with 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 Emax values, EC50 values being weakly affected. Similar results were obtained in guinea pig. In contrast, with two electrical depolarizations or with two different depolarizations (K+ followed by electrical), the NT effect during the second depolarization was not significantly affected. Concerning NT ant...Continue Reading
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Neurotensin modulates dopamine neurotransmission at several levels along brain dopaminergic pathways
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