ArticleNaunyn-Schmiedeberg's archives of pharmacology1996
Alpha 2-autoreceptors and alpha 2-heteroreceptors modulating tyrosine and tryptophan hydroxylase activity in the rat brain in vivo: an investigation into the alpha 2-adrenoceptor subtypes.
Article in Naunyn-Schmiedeberg's archives of pharmacology, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed, 38 citations in OpenAlex.
- Therapeutic Potential of Selectively Targeting the αFrontiers in psychiatry · 2017Review
- Chronic treatment and withdrawal of the cannabinoid agonist WIN 55,212-2 modulate the sensitivity of presynaptic receptors involved in the regulation of monoamine syntheses in rat brain.Naunyn-Schmiedeberg's archives of pharmacology · 2009Article
- Brain alpha(2)-adrenoceptors in monoamine-depleted rats: increased receptor density, G coupling proteins, receptor turnover and receptor mRNA.British journal of pharmacology · 2001Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The subtype determination of auto- and hetero-alpha 2-adrenoceptors modulating the synthesis of noradrenaline (NA) and serotonin (5-HT), respectively, was assessed using the accumulation of 3,4-dihydroxyphenylalanine (dopa) and 5-hydroxytryptophan (5-HTP) after decarboxylase inhibition as a measure of the rate of tyrosine and tryptophan hydroxylation in the rat brain in vivo. In the cerebral cortex and hippocampus, Org 3770 (non-selective alpha 2-adrenoceptor antagonist, 0.5-10 mg/kg, i.p.) increased (43%-58%) and clonidine (non-selective alpha 2-adrenoceptor agonist, 1 mg/kg) decreased (37%-49%) the synthesis of dopa. Also the antagonist ARC 239 (alpha 2B/C selective, 5-40 mg/kg) increased the synthesis of dopa in cortex (39%-46%) and hippocampus (17%-85%). In contrast, the antagonist BRL 44408 (alpha 2D selective, 1-10 mg/kg) did not increase the synthesis of dopa in cortex, and increased it modestly in hippocampus only. The agonist guanoxabenz (alpha 2B/C selective, 0.03-3 mg/kg) decreased the synthesis of dopa in both brain regions (20%-65%), whereas the agonist oxymetazoline (alpha 2D selective, 0.1-3 mg/kg) failed to do so. These results indicated that the alpha 2-autoreceptors that modulate the synthesis of dopa/NA are probably associated with the alpha 2B/C-subtypes. In cortex and hippocampus, clonidine decreased (35%-53%) the synthesis of 5-HTP but Org 3770 failed to induce the opposite effect (except the 2 mg/kg dose in cortex). BRL 44408 markedly increased the synthesis of 5-HTP in cortex (113%-148%) but not in hippocampus. Similarly, also ARC239 increased the formation of 5-HTP in cortex (36%-48%) but not in hippocampus, where it was decreased (30%-55%). Oxymetazoline decreased the synthesis of 5-HTP in hippocampus (28%-30%) but failed to do so in cortex. Guanoxabenz in the low dose range (0.03-0.3 mg/kg) did not decrease the synthesis of 5-HTP in any brain region. These results indicated that the alpha 2-heteroreceptors that modulate the synthesis of 5-HTP/5-HT may well be different from the proposed alpha 2B/C-autoreceptors modulating the synthesis of dopa/NA. These alpha 2-heteroreceptors appear to be associated with the alpha 2D-subtype.
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