TY - JOUR
T1 - Neuroleptic drug treatment alters in vitro central neurotensin metabolism
AU - Davis, Thomas P.
AU - Culling-Berglund, Alison
N1 - Funding Information:
We thank Dr. Jan vail Nispen, Organon International, Oss, The Netherlands, for his helpful suggestions and the Robert S. Flinn Medical Foundation for supporting this research.
PY - 1987
Y1 - 1987
N2 - Neurotensin (NT) has been shown to possess pharmacological properties associated with neuroleptic drugs. To determine if chronic haloperidol (HL; 3.5 mg/kg/day) or chlorpromazine (CPZ; 4.2 mg/kg/day) treatment affects central NT metabolism, HL and CPZ were perfused via Alzet® minipumps into male Sprague-Dawley rats for 8 days. Purified synaptosomal plasma membranes (pSPM) were isolated and time-course incubated with NT (100 μM; 30-120 min). All samples were analyzed by high resolution, reversed-phase high performance liquid chromatography. HL and CPZ caused an increase in NT metabolism at the pSPM. Although an increase in NT metabolism would result in a loss of biological activity, it does lead to a significant accumulation of the biologically active NT fragment NT-(9-13), which has been shown to bind to the NT receptor. Therefore, neuroleptic drug treatment alters NT metabolism at the pSPM, leading to the formation of a fragment with antinociceptive activity.
AB - Neurotensin (NT) has been shown to possess pharmacological properties associated with neuroleptic drugs. To determine if chronic haloperidol (HL; 3.5 mg/kg/day) or chlorpromazine (CPZ; 4.2 mg/kg/day) treatment affects central NT metabolism, HL and CPZ were perfused via Alzet® minipumps into male Sprague-Dawley rats for 8 days. Purified synaptosomal plasma membranes (pSPM) were isolated and time-course incubated with NT (100 μM; 30-120 min). All samples were analyzed by high resolution, reversed-phase high performance liquid chromatography. HL and CPZ caused an increase in NT metabolism at the pSPM. Although an increase in NT metabolism would result in a loss of biological activity, it does lead to a significant accumulation of the biologically active NT fragment NT-(9-13), which has been shown to bind to the NT receptor. Therefore, neuroleptic drug treatment alters NT metabolism at the pSPM, leading to the formation of a fragment with antinociceptive activity.
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U2 - 10.1016/0306-4530(87)90049-7
DO - 10.1016/0306-4530(87)90049-7
M3 - Article
C2 - 3659226
AN - SCOPUS:0023224809
SN - 0306-4530
VL - 12
SP - 253
EP - 260
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
IS - 4
ER -