BIOMAT Database Logo BIOMAT Database Logo

Effects of intranigral substance P and neurokinin A on striatal dopamine release--I. Interactions with substance P antagonists. 1990

M S Reid, and M Herrera-Marschitz, and T Hökfelt, and M Ohlin, and K L Valentino, and U Ungerstedt
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.

The functional role of striatonigral neurokinins were studied by analysing the effects of intranigral injections of substance P and neurokinin A on the extracellular level of dopamine and dihydroxyphenylacetic acid in the striatum, as measured by in vivo microdialysis in rats. Two substance P antagonists, substance P D-Pro2 D-Trp7,9 and substance P D-Arg1 D-Trp7,9 Leu11 were tested and analysed for their ability to block the neurokinin effects. Unilateral injections of substance P (0.00007-7.0 nmol injected in 0.2 microliter) as well as neurokinin A (0.009-9.0 nmol) into the substantia nigra, pars reticulata of halothane anaesthetized rats produced long-lasting increases in ipsilateral striatal dopamine and dihydroxyphenylacetic acid levels. The dose-response relationship for substance P on dopamine was biphasic, with maximal effects occurring after the middle dose (0.007-0.07 nmol). The dose-response relationship for neurokinin A was monophasic. Intranigral injections of substance P D-Pro2 D-Trp7,9 (0.07-0.7 nmol) or substance P D-Arg1 D-Trp7,9 Leu11 (0.07-0.7 nmol) produced a decrease in striatal dopamine, but an increase in striatal dihydroxyphenylacetic acid. At a low dose (0.07 nmol) substance P D-Pro2 D-Trp7,9 enhanced the dopamine increase produced by intranigral substance P (0.07 nmol) or neurokinin A (0.09), while at a high dose (0.7 nmol) it blocked both substance P and neurokinin A effects. Both doses of substance P D-Arg1 D-Trp7,9 Leu11 (0.07 and 0.7 nmol) blocked the substance P- but not the neurokinin A-induced increase in striatal dopamine. Immunohistochemical analysis revealed that high doses of substance P (7.0 nmol) and neurokinin A (0.9 and 9.0 nmol), as well as substance P D-Pro2 D-Trp7,9 and substance P D-Arg1 D-Trp7,9 Leu11 (0.07 and 0.7 nmol), induced a restricted loss of tyrosine hydroxylase in dendrites and cells, and neuropeptide K in terminals, at the site of injection. Further analysis shows that co-administration of substance P (0.07 nmol) or neurokinin A (0.09 nmol) did not modify the extent of the depletion of both immunoreactivities induced by substance P D-Arg1 D-Trp7,9 Leu11 (0.7 nmol). The extent of the effect produced by substance P D-Arg1 D-Trp7,9 Leu11 (0.7 nmol) was, however, smaller than the spread of intranigral injection of [125I]Bolton-Hunter-labelled substance P D-Arg1 D-Trp7,9 Leu11, and it is suggested that the "neurotoxic" effects of the substance P antagonists are not primarily involved in their abilities to inhibit striatal dopamine release and block the stimulation of dopamine after intranigral substance P and neurokinin A.(ABSTRACT TRUNCATED AT 400 WORDS)

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008297 Male Males
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D003342 Corpus Striatum Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE. Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D004298 Dopamine One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action. Hydroxytyramine,3,4-Dihydroxyphenethylamine,4-(2-Aminoethyl)-1,2-benzenediol,Dopamine Hydrochloride,Intropin,3,4 Dihydroxyphenethylamine,Hydrochloride, Dopamine
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D005110 Extracellular Space Interstitial space between cells, occupied by INTERSTITIAL FLUID as well as amorphous and fibrous substances. For organisms with a CELL WALL, the extracellular space includes everything outside of the CELL MEMBRANE including the PERIPLASM and the cell wall. Intercellular Space,Extracellular Spaces,Intercellular Spaces,Space, Extracellular,Space, Intercellular,Spaces, Extracellular,Spaces, Intercellular
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013373 Substance P An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of PAIN, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. Euler-Gaddum Substance P,Hypothalamic Substance P,SP(1-11),Euler Gaddum Substance P,Substance P, Euler-Gaddum,Substance P, Hypothalamic

Related Publications

M S Reid, and M Herrera-Marschitz, and T Hökfelt, and M Ohlin, and K L Valentino, and U Ungerstedt
Intranigral injection of dynorphin in combination with substance P on striatal dopamine metabolism in the rat.
March 1988, Brain research,
M S Reid, and M Herrera-Marschitz, and T Hökfelt, and M Ohlin, and K L Valentino, and U Ungerstedt
Intranigral GABAergic drug effects on striatal dopamine activity.
April 1989, Pharmacology, biochemistry, and behavior,
M S Reid, and M Herrera-Marschitz, and T Hökfelt, and M Ohlin, and K L Valentino, and U Ungerstedt
Intranigral application of substance P antagonists prevents the haloperidol-induced activation of striatal tyrosine hydroxylase.
May 1984, Naunyn-Schmiedeberg's archives of pharmacology,
M S Reid, and M Herrera-Marschitz, and T Hökfelt, and M Ohlin, and K L Valentino, and U Ungerstedt
Substance P fragments and striatal endogenous dopamine outflow: interaction with substance P.
December 1998, Neuropeptides,
M S Reid, and M Herrera-Marschitz, and T Hökfelt, and M Ohlin, and K L Valentino, and U Ungerstedt
Sequence-specific effects of neurokinin substance P on memory, reinforcement, and brain dopamine activity.
January 1993, Psychopharmacology,
M S Reid, and M Herrera-Marschitz, and T Hökfelt, and M Ohlin, and K L Valentino, and U Ungerstedt
The effects of neurokinin A, neurokinin B, and eledoisin on substance P analysis.
April 1991, Journal of clinical monitoring,
M S Reid, and M Herrera-Marschitz, and T Hökfelt, and M Ohlin, and K L Valentino, and U Ungerstedt
Intranigral injection of selective neurokinin-1 and neurokinin-3 but not neurokinin-2 receptor agonists biphasically modulate striatal dopamine metabolism but not striatal preprotachykinin-A mRNA in the rat.
July 1993, Neuroscience letters,
M S Reid, and M Herrera-Marschitz, and T Hökfelt, and M Ohlin, and K L Valentino, and U Ungerstedt
D-Amphetamine reduces striatal substance P concentrations by presynaptic release of dopamine.
March 1980, Brain research,
M S Reid, and M Herrera-Marschitz, and T Hökfelt, and M Ohlin, and K L Valentino, and U Ungerstedt
Effects of intranigral injection of taurine and GABA on striatal dopamine release monitored voltammetrically in the unanaesthetized rat.
September 1986, Brain research,
M S Reid, and M Herrera-Marschitz, and T Hökfelt, and M Ohlin, and K L Valentino, and U Ungerstedt
Acute effects of intranigral application of MPP+ on nigral and bilateral striatal release of dopamine simultaneously recorded by microdialysis.
January 1991, Brain research,
Copied contents to your clipboard!