Intranigral substance P modulation of striatal dopamine: interaction with N-terminal and C-terminal substance P fragments.
The effects of unilateral injections of two substance P fragments, the N-terminal substance P (1-7) (SP1-7) and the C-terminal substance P (6-11) (SP6-11) into the substantia nigra, pars reticulata on dopamine (DA) release in the ipsilateral striatum of halothane-anaesthetized rats were studied using microdialysis. SP1-7 and SP6-11 were also tested for their ability to modify the DA stimulation produced by intranigral injections of SP or neurokinin A (NKA). In addition, the SP antagonist Spantide I was tested for its ability to modify the DA stimulation produced by an intranigral injection of SP1-7. Intranigral injections of SP1-7 (0.001-5.0 nmol) inhibited DA release after low doses (0.001-0.01 nmol), but stimulated DA release after high doses (0.1-5.0 nmol). Striatal dihydroxyphenylacetic acid (DOPAC) levels increased moderately after high doses of SP1-7 (1.0-5.0 nmol). Intranigral injections of SP6-11 (0.01-5.0 nmol) inhibited DA release, but enhanced striatal DOPAC levels, dose-dependently. SP1-7 (0.01-0.1 nmol), but not SP6-11 (0.1 nmol), blocked the stimulation of striatal DA release produced by intranigral SP (0.07 nmol). Neither SP1-7 (0.1 nmol) nor SP6-11 (0.1 nmol) could modify the stimulation of striatal DA release produced by intranigral NKA (0.09 nmol). The increase in DA release after a high dose of SP1-7 (1.0 nmol) was not modified by co-administration with Spantide I (0.07 nmol).(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
M S
MS
Reid
M
M
Herrera-Marschitz
L
L
Terenius
U
U
Ungerstedt
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007267:Injections; D008297:Male; D015288:Neurokinin A / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology*; D013378:Substantia Nigra
D010446:Peptide Fragments; D013373:Substance P; C032292:substance P (6-11); C036877:substance P (1-7); D015288:Neurokinin A; C042867:spantide; D011761:Pyrrolidonecarboxylic Acid; D004298:Dopamine