The pharmacology of neurotensin analogues on neurones in the rat substantia nigra, pars compacta in vitro.
The effects of neurotensin and neurotensin analogues on dopamine neurones were studied in an in vitro slice preparation of rat substantia nigra, pars compacta using extracellular and intracellular recording techniques. Neurotensin had an EC50 of 13 nM in these experiments. This study showed that the C-terminal 5 amino acids of neurorotensin in neurotensin-(9-13) retained agonist activity on substantia nigra neurones. The naturally occurring neurotensin analogues neuromedin N and avian neurotensin were also active whilst kinetensin was inactive. Kinetensin differs from the C-terminal neurotensin 5-amino acids by two amino acids. The difference between the activity of neurotensin and the inactivity of kinetensin was investigated using synthetic peptides which contained single amino acid substitutions. These results show that position 12 of neurotensin is important for agonist activity in the substantia nigra.
Parke-Davis Neuroscience Research Centre, Addenbrookes Hospital Site, Cambridge, UK.
K D
KD
Keegan
G N
GN
Woodruff
R D
RD
Pinnock
D000818:Animals; D001717:Birds; D004298:Dopamine / Q000378:metabolism; D004594:Electrophysiology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009496:Neurotensin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects*
D009842:Oligopeptides; D010446:Peptide Fragments; C042090:neuromedin N; C048812:kinetensin; D009496:Neurotensin; D004298:Dopamine