THE PHARMACOLOGY OF NEUROTENSIN ANALOGS ON NEURONS IN THE RAT SUBSTANTIA-NIGRA, PARS COMPACTA IN-VITRO

The effects of neurotensin and neurotensin analogues on dopamine neuro nes were studied in an in vitro slice preparation of rat substantia ni gra, pars compacta using extracellular and intracellular recording tec hniques. Neurotensin had an EC(50) of 13 nM in these experiments. This study showed that the C-terminal 5 amino acids of neurorotensin in ne urotensin-(9-13) retained agonist activity on substantia nigra neurone s. The naturally occurring neurotensin analogues neuromedin N and avia n neurotensin were also active whilst kinetensin was inactive. Kineten sin differs from the C-terminal neurotensin 5-amino acids by two amino acids. The difference between the activity of neurotensin and the ina ctivity of kinetensin was investigated using synthetic peptides which contained single amino acid substitutions. These results show that pos ition 12 of neurotensin is important for agonist activity in the subst antia nigra.