Effects of intranigral substance P and neurokinin A on striatal dopamine release--I. Interactions with substance P antagonists.
(1990) In Neuroscience 36(3). p.643-658- Abstract
- 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 Pd-Pro2d-Trp7,9 and substance Pd-Arg1d-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 μl) 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.... (More) - 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 Pd-Pro2d-Trp7,9 and substance Pd-Arg1d-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 μl) 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 Pd-Pro2d-Trp (0.07–0.7 nmol) or substance Pd-Arg1d-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 Pd-Pro2d-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 Pd-Arg1d-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 substanced-Arg1d-Trp7,9 and substance Pd-Arg1d-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 Pd-Arg1d-Trp7,9 Leu11 (0.7 nmol). The extent of the effect produced by substance Pd-Arg1d-Trp7,9 Leu11 (0.7 nmol) was, however, smaller than the spread of intranigral injection of [125I]Bolton-Hunter-labelled substance Pd-Arg1d-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. We propose that striatonigral substance P and neurokinin A produce a tonic excitatory modulation of nigrostriatal dopamine via neurokinin receptors which can be blocked by substance Pd-Arg1d-Trp7,9. However, substance P and neurokinin A are probably acting via different receptors since substance Pd-Arg1d-Trp7,9 Leu11 blocked substance P but not neurokinin A stimulation of striatal dopamine release.
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- author
- Reid, M.S. ; Herrera-Marschitz, M. ; Hökfelt, T. ; Ohlin, M. LU ; Valentino, K.L. and Ungerstedt, U.
- publishing date
- 1990
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Neuroscience
- volume
- 36
- issue
- 3
- pages
- 643 - 658
- publisher
- Elsevier
- external identifiers
-
- scopus:0025042666
- ISSN
- 1873-7544
- DOI
- 10.1016/0306-4522(90)90007-Q
- language
- English
- LU publication?
- no
- id
- 1f8cdee8-4147-4d16-81f6-86ff32b12ee7
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- 2022-12-05 08:26:13
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- 2024-01-03 18:38:44
@article{1f8cdee8-4147-4d16-81f6-86ff32b12ee7, abstract = {{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 Pd-Pro2d-Trp7,9 and substance Pd-Arg1d-Trp7,9 Leu11 were tested and analysed for their ability to block the neurokinin effects.<br/><br/>Unilateral injections of substance P (0.00007–7.0 nmol injected in 0.2 μl) 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 Pd-Pro2d-Trp (0.07–0.7 nmol) or substance Pd-Arg1d-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 Pd-Pro2d-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 Pd-Arg1d-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 substanced-Arg1d-Trp7,9 and substance Pd-Arg1d-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 Pd-Arg1d-Trp7,9 Leu11 (0.7 nmol). The extent of the effect produced by substance Pd-Arg1d-Trp7,9 Leu11 (0.7 nmol) was, however, smaller than the spread of intranigral injection of [125I]Bolton-Hunter-labelled substance Pd-Arg1d-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. We propose that striatonigral substance P and neurokinin A produce a tonic excitatory modulation of nigrostriatal dopamine via neurokinin receptors which can be blocked by substance Pd-Arg1d-Trp7,9. However, substance P and neurokinin A are probably acting via different receptors since substance Pd-Arg1d-Trp7,9 Leu11 blocked substance P but not neurokinin A stimulation of striatal dopamine release.<br/><br/>}}, author = {{Reid, M.S. and Herrera-Marschitz, M. and Hökfelt, T. and Ohlin, M. and Valentino, K.L. and Ungerstedt, U.}}, issn = {{1873-7544}}, language = {{eng}}, number = {{3}}, pages = {{643--658}}, publisher = {{Elsevier}}, series = {{Neuroscience}}, title = {{Effects of intranigral substance P and neurokinin A on striatal dopamine release--I. Interactions with substance P antagonists.}}, url = {{http://dx.doi.org/10.1016/0306-4522(90)90007-Q}}, doi = {{10.1016/0306-4522(90)90007-Q}}, volume = {{36}}, year = {{1990}}, }