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PubMed1992

Regulation of the chromaffin granule catecholamine transporter in cultured bovine adrenal medullary cells: stimulus-biosynthesis coupling.

The transsynaptic induction of the monoamine transporter present on the membrane of chromaffin granules was studied in primary cultures of dissociated bovine adrenomedullary cells submitted to a chronic secretory stimulation. The amount of the vesicular monoamine transporter was assayed by binding of the specific ligand [3H]-dihydrotetrabenazine. After several days of incubation in the presence of high potassium, the concentration of [3H]-dihydrotetrabenazine binding sites was increased by a 1.5-2.5 factor. This increase was smaller in the presence of the cholinergic agonist carbachol. The long-term inductions of the vesicular monoamine transporter, of tyrosine hydroxylase, and of acetylcholinesterase were of similar magnitude. Under the same conditions, we found no variation in either the activities of other catecholamine biosynthetic enzymes (dopamine beta-hydroxylase and DOPA decarboxylase), or in metabolic enzymes such as lactate dehydrogenase and cytochrome c oxidase, and a decrease in the cellular content of chromogranin A and cytochrome b-561. The induction of the vesicular monoamine transporter was inhibited by the calcium channel antagonists, fluspirilene and nifedipine, and was increased by the agonist Bay K 8644. It was abolished by cycloheximide and actinomycin D. These results indicate that calcium entry into chromaffin cells increases the synthesis of the vesicular monoamine transporter, presumably by transcriptional activation. Elevation of intracellular cyclic AMP concentration or activation of protein kinase C also induced an increase in the expression of the vesicular monoamine transporter. Our results confirm that components of storage vesicle membranes are differentially regulated in response to secretory stimulation, as are several cytosolic or intravesicular soluble proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1982

Striatal dopamine autoreceptors uninfluenced by chronic administration of antidepressants.

Dopamine (DA) receptor sensitivity to apomorphine (APO) was assessed in the rat nigrostriatal system following chronic antidepressant treatment. Imipramine (IMI), iprindole (IPR) or vehicle was administered to rats for 10 days (10 mg/kg i.p., b.i.d.). Two and a half days after the last injection 3,4-dihydroxyphenylacetic acid (DOPAC) levels were measured in rat striata following injection of APO (50 or 100 micrograms/kg s.c.) or vehicle. In contrast with rats receiving chronic vehicle injections, rats chronically treated with IMI or IPR failed to exhibit a significant APO-induced fall in striatal DOPAC levels. Antidepressant-treated animals, however, exhibited significantly lower basal DOPAC levels than vehicle-treated rats. In an effort to localize the diminished APO response, DA autoreceptor sensitivity to APO was assessed in drug- and vehicle-treated animals. Employing gamma-butyrolactone (GBL) and a dihydroxyphenylalanine (DOPA) decarboxylase inhibitor to elevate striatal DOPA, the APO-induced reversal of DOPA elevation was used as an index of DA autoreceptor sensitivity. This GBL-stimulated in vivo tyrosine hydroxylation was similarly reversed by APO (125, 250 or 500 micrograms/kg i.p.) in IMI-, IPR- and vehicle-treated animals. In view of these findings, we propose that the blunted biochemical response to APO observed in animals pretreated with antidepressants does not originate as a result of alterations in the sensitivity of DA autoreceptors located on the striatal presynaptic nerve terminal.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1979

[Relationship between gnawing compulsion and central dopaminergic mechanism in guinea pigs (author's transl)].

It has been reported that an increased in dopaminergic activity in the striatum can induce gnawing compulsion, a stereotyped behavior. Apomorphine, amphetamine and L-DOPA also produce such effects, particularly in the rat. However, it has been reported that the gnawing compulsion in the guinea pig cannot be induced with L-DOPA and is not related to the levels of catecholamine in the brain. It is of essential importance in this kind of research to clarify whether or not a dopaminergic mechanism is equally involved in gnawing compulsion of the rodent in general. The present study dealt with the mechanism of gnawing compulsion with L-DOPA administration to guinea pigs. Gnawing compulsion was amplified by crystal pick-up and amplifiers and was continuously recorded by an inkwriting-oscilloscope. The recorded data were scored for quantitative and objective analysis. Certainly, L-DOPA alone did not induce continuous gnawing, but the gnawing was obviously induced by pretreatment with benserazide, a peripheral decarboxylase inhibitor. The induced gnawing complusion was inhibited by pimozide and haloperidol which are both dopamine receptor blockers. When catecholamine synthesis was inhibited pretreatment with alpha-methyl-p-tyrosine, the amphetamine induced gnawing compulsion alone was markedly inhibited, but the apomorphine or L-DOPA induced gnawing compulsion following the pretreatment with benserazide was not inhibited. Therefore, it was deduced that gnawing compulsion was induced with amphetamine directly by dopamine release, with apomorphine by its direct stimulation of the dopamine receptor, and with L-DOPA by its action on the dopamine receptor, after having been converted to dopamine. Based on these results, it was concluded that the dopaminergic mechanism is closely involved in gnawing compulsion seen in the guinea pig as well as in the rat.

Amphetamine↗
PubMed1986

Coexistence of galanin-like immunoreactivity with catecholamines, 5-hydroxytryptamine, GABA and neuropeptides in the rat CNS.

The coexistence of galanin (GAL)-like immunoreactivity (LI) with markers for catecholamines, 5-hydroxytryptamine (5-HT), GABA, or some neuropeptides was mapped in the rat CNS by using adjacent sections, as well as by elution-restaining and double-labeling immunocytochemistry. Many instances of coexistence were observed, but there were also numerous GAL-positive cell body populations displaying distributions similar to those of these markers but without apparent coexistence. In the hypothalamic arcuate nucleus GAL-LI was found in a large proportion of tyrosine hydroxylase (TH)-positive cell bodies (A12 cells), both in the dorsomedial and ventrolateral subdivisions, with a higher number in the latter. GAL-LI coexisted in glutamic acid decarboxylase (GAD)-positive somata in the posterior aspects of the arcuate nucleus and at all rostrocaudal levels in fibers in the external layer of the median eminence. In the anterior hypothalamus, a large population of the cells of the parvocellular and magnocellular paraventricular nuclei contained both GAL-LI and vasopressin-LI. Moreover, somata containing both GAD- and GAL-LI were seen lateral to the mammillary recess in the tuberal and caudal magnocellular nuclei. Some of the neurons of the caudal group were shown to project to the occipital cortex using combined retrograde tracing and immunofluorescence. With regard to mesencephalic and medullary catecholamine neurons, GAL-LI coexisted in a large proportion of the noradrenergic locus coeruleus somata (A6 cell group) and in the A4 group dorsolateral to the fourth ventricle, as well as in the caudal parts of the A2 group in the dorsal vagal complex. However, in more rostral parts of the latter, especially in the medial subdivision of the solitary tract nucleus, a very large population of GAL-IR small cell bodies was seen intermingling with catecholamine neurons, but they did not contain TH-LI. Furthermore, GAL-IR cell bodies coextensive with, but not coexisting in, TH-IR somata were seen in the C1 (epinephrine) horea in the ventrolateral medulla at the level of area postrema and in the most rostral aspects of the C1 group. Finally, 5-HT-positive cell bodies of the mesencephalic and medullary raphe nuclei and a subpopulation of coarse 5-HT nerve fibers in the hippocampus co-contained GAL-LI. The present results demonstrate that a GAL-like peptide is present in many systems containing other neuroactive compounds, including dopamine, norepinephrine, 5-HT, GABA, and vasopressin.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1981

DOPA in sympathetic nerve tissue--a possible source of serum DOPA in albino animals.

Dopa, catecholamines, and dopac were determined in superior cervical ganglia of albino rats. The average amount of dopa in ganglia of control animals was 1.1--1.6 micrograms/g. The concentrations of catecholamines and dopac were similar to values reported by others. The tyrosine hydroxylase inhibitor alpha-methylparatyrosine methyl ester caused marked decrease in the dopa concentration in the ganglia. The effect of reserpine was less pronounced. The aromatic amino acid decarboxylase inhibitor NSD 1015 markedly increased the dopa concentration.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

Effects of hydrastine derivatives on dopamine biosynthesis in PC12 cells.

The effects of hydrastine derivatives on dopamine biosynthesis in PC12 cells were investigated. Treatments of PC12 cells with (1R,9S)-beta-hydrastine hydrochloride [(+)-beta-hydrastine HCl] and (1R,9S)-beta-hydrastine [(-)-beta-hydrastine] showed 50.6 % and 33.1 % inhibition of dopamine content at a concentration of 10 microM for 48 h. However, (1S,9R)-beta-hydrastine [(+)-beta-hydrastine] and hydrastinine hydrochloride did not reduce dopamine content. The IC(50) values of (1R,9S)-beta-hydrastine hydrochloride and (1R,9S)-beta-hydrastine were 9.3 microM and 20.7 microM , respectively. Next, the intracellular mechanisms of (1R,9S)-beta-hydrastine hydrochloride in PC12 cells were investigated. Dopamine content decreased at 6 h and reached a minimal level at 24 h after the exposure of PC12 cells to 20 microM (1R,9S)-beta-hydrastine hydrochloride. Tyrosine hydroxylase (TH) activity was inhibited at 6 h following the treatment with (1R,9S)-beta-hydrastine hydrochloride, and was maintained at a reduced level for up to 36 h in PC12 cells (17 - 27 % inhibition at 20 microM), whereas TH mRNA level was not found to alter for 24 h. However, the level of intracellular Ca++ concentration decreased by treatment with (1R,9S)-beta-hydrastine hydrochloride at 20 microM by 18.4 % inhibition relative to the control level in PC12 cells. These results suggest that (1R,9S)-beta-hydrastine hydrochloride contributes partially to the decrease in dopamine content by the inhibition of TH activity in PC12 cells.

Alkaloids↗
PubMed2003

Age-related irreversible progressive nigrostriatal dopaminergic neurotoxicity in the paraquat and maneb model of the Parkinson's disease phenotype.

While advancing age is the only unequivocally accepted risk factor for idiopathic Parkinson's disease, it has been postulated that exposure to environmental neurotoxicants combined with ageing could increase the risk for developing Parkinson's disease. The current study tested this hypothesis by exposing C57BL/6 mice that were 6 weeks, 5 months or 18 months old to the herbicide paraquat, the fungicide maneb or paraquat + maneb, a combination that produces a Parkinson's disease phenotype in young adult mice. Paraquat + maneb-induced reductions in locomotor activity and motor coordination were age dependent, with 18-month-old mice most affected and exhibiting failure to recover 24 h post-treatment. Three months post-treatment, reductions in locomotor activity and deficits in motor coordination were sustained in 5-month-old and further reduced in 18-month-old paraquat + maneb groups. Progressive reductions in dopamine metabolites and dopamine turnover were greatest in 18-month-old paraquat + maneb and paraquat groups 3 months post-treatment. Increased tyrosine hydroxylase enzyme activity compensated for striatal tyrosine hydroxylase protein and/or dopamine loss following treatment in 6-week-old and 5-month-old, but not 18-month-old paraquat and paraquat + maneb mice. Numbers of nigrostriatal dopaminergic neurons were reduced in all age groups following paraquat alone and paraquat + maneb exposure, but these losses, along with decreases in striatal tyrosine hydroxylase protein levels, were progressive in 18-month-old paraquat and paraquat + maneb groups between 2 weeks and 3 months post-exposure. Collectively, these data demonstrate enhanced sensitivity of the ageing nigrostriatal dopamine pathway to these pesticides, particularly paraquat + maneb, resulting in irreversible and progressive neurotoxicity.

Aging↗
PubMed1983

Hypophysectomy-induced striatal hypersensitivity and mesolimbic hyposensitivity to apomorphine.

Seven days post-hypophysectomy female rats display a hyposensitivity to the locomotor effects of apomorphine and a hypersensitivity to the stereotypy effects of apomorphine, while at 28 days post-hypophysectomy they are hypersensitive to both the locomotor and stereotypy effects of apomorphine. The hyposensitivity to the locomotor effects, at 7 days post-hypophysectomy, was associated with a decrease in 3H-spiroperidol binding and an increase in tyrosine hydroxylase activity in the nucleus accumbens septi, whereas the hypersensitivity, at 28 days post-hypophysectomy, was associated with an increase in 3H-spiroperidol and a decrease in tyrosine hydroxylase activity in the n. accumbens septi. The increased apomorphine-induced stereotypy in both the 7 and 28 days post-hypophysectomized animals was related to an increased 3H-spiroperidol binding and a decreased tyrosine hydroxylase activity in the striatum. These behavioral and neurochemical data demonstrate that following hypophysectomy female rats will develop a transient decrease in dopamine receptor sensitivity in the n. accumbens septi, while the dopamine sensitivity in the striatum is increased. Thus the hypophysectomized female rat may prove to be a valuable model to study these two separate dopamine systems and their possible modulatory roles in the display of various behaviors.

Animals↗
PubMed1980

Depression of sympathetic nervous function by DL-alpha-monofluoromethyldopa, an enzyme-activated, irreversible inhibitor of L-aromatic amino acid decarboxylase.

We investigated the effects on peripheral sympathetic nervous function of monofluoromethyldopa (MFMD, RMI 71963), a selective, enzyme-activated, irreversible inhibitor of L-aromatic amino acid decarboxylase. Three daily injections of 2.5, 25, or 100 mg/kg MFMD to rats reduced the dopamine and norepinephrine concentrations in the heart and increased those of L-dopa. Sedation was seen with the two highest doses of MFMD. Cardiovascular responses in the pithed rat to stimulation of the whole spinal sympathetic outflow and to injections of tyramine were reduced by treatment with MFMD. Both the reduced sympathetic function and the depleted transmitter store were restored by infusions of dopamine. Norepinephrine depletion and functional inhibition were obtained with smaller doses of MFMD (3, 6, and 10 mg/kg daily) given for longer periods (10 days). Blood pressure in spontaneously hypertensive rats was reduced by treatment with MFMD, 25 mg/kg, daily for 3 days. In vitro responses to nerve stimulation of portal veins declined during incubation with MFMD or alpha-methyl-p-tyrosine; responses of atria were unaffected. Changes in norepinephrine concentrations of portal veins and atria closely paralleled the changes in function. MFMD is the first compound which depletes peripheral norepinephrine concentrations by inhibiting transmitter biosynthesis at the decarboxylase step. Such depletion results in inhibition of sympathetic function in vivo and introduces a novel approach to pharmacological manipulation of the activity of the peripheral sympathetic nervous system.

Animals↗
PubMed1986

Regulation of dopamine synthesis in the medial prefrontal cortex is mediated by release modulating autoreceptors: studies in vivo.

Previous studies have suggested that rat mesoprefrontal dopamine (DA) neurons are devoid of synthesis and impulse-modulating autoreceptors. We have examined further the presynaptic regulatory parameters of these neurons in vivo and have developed a model based on the following observations. Prefrontal DA turnover, measured as the rate of DA disappearance after inhibition of tyrosine-3-monooxygenase by alpha-methyltyrosine, is relatively rapid (T1/2 = 15 min) and is suppressed by apomorphine (50 micrograms/kg) pretreatment, suggesting that prefrontal DA release is sensitive to regulation by DA agonists. Prefrontal DOPA accumulation (measured after inhibition of decarboxylase with m-hydroxybenzylamine) is also diminished after administration of DA agonists, such as apomorphine, BHT-920, 3-[4-(4-phenyl)-1,2,3,6-tetrahydropyridyl-1] butyl indole (EMD 23 448) and 3-(3-hydroxyphenyl)-N-n-propylpiperidine[(+)-3-PPP]. However, the apomorphine-induced inhibition of prefrontal, but not striatal, DOPA synthesis is blocked by either cessation of impulse-dependent DA release (after gamma-butyrolactone) or by depletion of intraneuronal DA (after reserpine), suggesting that DA agonists affect prefrontal DA synthesis only in the presence of DA release. Inhibition of impulse flow after administration of gamma-butyrolactone does not increase the rate of prefrontal tyrosine hydroxylation in vivo, suggesting that synaptic DA does not influence medial prefrontal DA synthesis under basal conditions. After treatment with m-hydroxybenzylamine (30 min), prefrontal DA levels are substantially reduced (-70%) and inhibition of prefrontal synthesis by DA agonists is associated with an increase in intraneuronal DA relative to m-hydroxybenzylamine-treated controls, suggesting that agonist-induced synthesis inhibition is a consequence of activation of release-modulating autoreceptors with a subsequent decrease in DA release and increase in end product inhibition of tyrosine hydroxylation. These and other data in the accompanying paper suggest that the nerve terminals of mesoprefrontal DA neurons are unique in their constitution of functional autoreceptors in that they contain only a release-modulating mechanism.

3,4-Dihydroxyphenylacetic Acid↗
PubMedDate not supplied

Role of tyrosine kinases in bombesin regulation of gastric mucosal proliferative activity in young and aged rats.

In vivo and in vitro experiments were performed to examine the responsiveness of the gastric mucosa to the growth-promoting action of bombesin in young (4 months) and aged (22 months) Fischer 344 rats. In addition, the role of tyrosine kinase (Tyr-K) in regulating this action of bombesin was also examined. In young rats, infusion of bombesin (300 ng/kg/h) by osmotic minipump for 2 weeks resulted in a significant 100% increase in mucosal DNA synthesis and ornithine decarboxylase (ODC) activity. These increases were accompanied by a 32% (p less than 0.025) rise in gastric mucosal overall Tyr-K activity and a 71% (p less than 0.001) increase in Tyr-k activity associated with pp60c-src, when compared with the corresponding controls. The bombesin-induced stimulation of pp60c-src Tyr-k activity was also associated with a 25% increase in phosphorylation of this protein. In contrast, in aged rats, none of these parameters were affected by bombesin. A similar phenomenon was also observed when mucosal explants from young and aged rats were exposed to bombesin in an organ culture system. Exposure of gastric mucosal explants from young, but not from aged, rats to 10(-8) M bombesin for 8 h resulted in a 300% (p less than 0.001) increase in ODC activity, a 150% (p less than 0.001) rise in Tyr-k activity, and a marked increase (400-600%) in tyrosine-specific phosphorylation of three membrane proteins with M(r) of 55, 44, and 41 kDa, when compared with the corresponding controls. However, these increases were totally abolished by genistein, a specific irreversible inhibitor of Tyr-k.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed2005

The inhibitory effects of deltamethrin on dopamine biosynthesis in rat PC12 cells.

The inhibitory effects of deltamethrin (DM) on dopamine biosynthesis in PC12 cells were investigated. Levels of dopamine in PC12 cells were detected after treatment with different doses from 10(-4)M to 10(-6)M deltamethrin or combined with 20 microM or 50 microM l-3,4-dihydroxyphenylalanine (L-Dopa) for 3 h or 12 h by HPLC. Flow cytometry (FCM) and RT-PCR technology were used to detect the levels of tyrosine hydroxylase (TH) mRNA and protein in PC12 cells treated with different doses of deltamethrin for 3 h or 12 h. Deltamethrin decreased the levels of dopamine, TH mRNA and TH protein in PC12 cells, and the increased dopamine levels induced by l-Dopa at 20-50 microM were also decreased by deltamethrin for 3 h or 12 h. These results indicate that deltamethrin decreases dopamine content by the inhibition of TH mRNA and protein level in PC12 cells and maybe also have inhibitory effect on aromatic l-amino acid decarboxylase.

Animals↗
PubMed1994

Evidence for protein kinase C involvement in the short-term activation by prolactin of tyrosine hydroxylase in tuberoinfundibular dopaminergic neurons.

The mechanism of the short-term activation by prolactin (PRL) of tyrosine hydroxylase (TH) in tuberoinfundibular dopaminergic neurons was examined in vitro on hypothalamic slices from ovariectomized rats. TH activity (determined by 3,4-dihydroxyphenylalanine accumulation in the median eminence after blockade of decarboxylase with NSD 1055) showed a dose-dependent increase within 2 h of incubation of the hypothalamic slices with PRL. To determine whether a phosphorylation process was involved in this increase in TH activity, we studied the sensitivity of the enzyme to dopamine (DA) feedback inhibition. In control median eminences, two kinetically different forms of TH coexisted, one exhibiting a Ki(DA) value of 29.92 +/- 0.49 microM, the other being approximately 15-fold more sensitive to DA inhibition with a Ki(DA) of 1.96 +/- 0.09 microM, likely corresponding to a phosphorylated and active form and to a nonphosphorylated and less active form, respectively. After PRL treatment, the TH form of low Ki(DA) remained unaffected, whereas the Ki(DA) of the purported active form of TH increased to 62.6 +/- 0.8 microM, suggesting an increase in the enzyme phosphorylation. This increase in the Ki(DA) of TH was selectively prevented by GF 109203X, a potent and selective inhibitor of protein kinase C, but not by a specific inhibitor of protein kinase A or calmodulin. Finally, this action of PRL could be mimicked by 12-O-tetradecanoylphorbol 13-acetate (a direct activator of protein kinase C). These results suggest that PRL, at the median eminence level, activates TH by increasing the enzyme phosphorylation and that this action may involve an activation of protein kinase C.

Animals↗
PubMed1986

Investigation of dopamine content, synthesis, and release in the rabbit retina in vitro: I. Effects of dopamine precursors, reserpine, amphetamine, and L-DOPA decarboxylase and monoamine oxidase inhibitors.

The basal catecholamine content of rabbit retina was determined by liquid chromatography with electrochemical detection (LC-EC) and 3,4-dihydroxyphenylethylamine (dopamine, DA) found to be the major catecholamine. The immediate DA precursor, 3,4-dihydroxyphenylalanine (L-DOPA), and the metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), were also detected at about 2.8% and 17% of DA levels, respectively. When added exogenously, L-tyrosine did not increase the rate of DA synthesis over the basal level. In contrast, exogenous L-DOPA led to a 3.5-fold increase in DA, and to a 20-fold increase in DOPAC content. The monoamine oxidase inhibitors pargyline and (-)-deprenyl differentially affected the degradation of DA, since 100 microM pargyline was apparently more effective than 100 microM (-)-deprenyl. Reserpine and (+/-)-amphetamine each induced a Ca2+-independent decrease of DA stores. The separate actions of reserpine and (+/-)-amphetamine in lowering tissue DA levels were additive, suggesting two separate pools of DA available for release from presynaptic stores. The present study demonstrates that the LC-EC technique may be used to investigate the modulation of the synthesis and release of retinal DA in vitro, without the prior uptake of radiolabelled transmitter.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Mass and in situ activity of tyrosine hydroxylase in the median eminence: effect of hyperprolactinemia.

The role of PRL in the control of catecholaminergic hypothalamic neurons of female rats was investigated. The in situ activity of tyrosine hydroxylase (TH) in neurites of these neurons was assayed by measuring the rate of accumulation of L-3,4-dihydroxyphenylalanine (DOPA) in the median eminence (ME) after the administration of a DOPA decarboxylase inhibitor. The mass of TH was measured by an immunoblot assay using rat TH as the standard. Hyperprolactinemia was induced by pituitaries implanted beneath a renal capsule. Hyperprolactinemia resulted in a significant increase in the in situ activity of TH without an increase in TH mass. The release of dopamine from hypothalamic neurons was assessed by measuring the concentration of dopamine in hypophysial portal plasma. The mean concentration of dopamine in portal plasma of rats bearing pituitary implants was 3 times that in controls. When circulating PRL was neutralized by administration of antiserum against rat PRL, the activity of TH was reduced significantly compared to that in animals treated with preimmune serum. In animals bearing pituitary implants, phosphorylation of TH in the ME was not different from that in control animals. We conclude that the biosynthetic and secretory activities of dopaminergic neurons of the hypothalamus are potentiated by PRL, but the potentiation is not due to an increase in the mass of TH or to the capacity of the neurites of the ME to phosphorylate TH.

Animals↗
PubMed1989

Immunocytochemical localization of L-glutamate decarboxylase and catecholamine-synthesizing enzymes in the retroperitoneal sympathetic tissue of the newborn rat.

The localization of L-glutamate decarboxylase (GAD), the enzyme synthesizing gamma-aminobutyric acid, was studied in newborn rat retroperitoneal sympathetic tissue, i.e. the main retroperitoneal paraganglion, adrenal medullae and abdominal sympathetic ganglia using the indirect immunofluorescence method. The coexistence of GAD with the catecholamine-synthesizing enzymes tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) was analyzed in consecutive sections or by staining one section consecutively with different antisera. GAD immunoreactivity was observed only in some cell types of each organ studied. In the main retroperitoneal paraganglion, the small, intensely TH-immunoreactive, paraganglion-type cells were GAD-immunoreactive, while the larger moderately TH-immunoreactive, neuron-like cells were non-reactive for GAD. In the adrenal medulla, GAD immunoreactivity was localized only in the adrenaline-synthesizing, PNMT-immunoreactive chromaffin cells. The noradrenaline-synthesizing, i.e. the TH-immunoreactive cells with no PNMT immunoreactivity, were non-reactive for GAD. In the abdominal sympathetic ganglia, some small intensely TH-immunoreactive cells were GAD-immunoreactive, while the principal neurons were non-reactive for GAD. These results provide immunohistochemical evidence that GAD is present and is colocalized with catecholamine-synthesizing enzymes in various sympathetic tissues of the newborn rat. The present results indicate that GAD is localized in adrenaline-synthesizing cells of all the sympathetic tissues studied. A fraction of noradrenaline-synthesizing cells of retroperitoneal sympathetic tissues, excluding the adrenal medulla, also contains GAD.

Adrenal Medulla↗
PubMed1976

Mechanisms of tyrosine hydroxylase and dopamine beta-hydroxylase induction in organ cultures of rat sympathetic ganglia by potassium depolarization and cholinomimetics.

It was the aim of the present study to elucidate the mechanisms involved in specific tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) induction by potassium depolarization and cholinomimetics in rat superior cervical ganglia kept in organ culture. The effect of high (54 mM) potassium concentration on intact ganglia seems to result in a dual action: a) a specific induction of TH and DBH via release of acetylcholine from preganglionic cholinergic nerve terminals. b) a non-specific effect on terminal adrenergic neurons resulting in a general increase of protein synthesis as indicated by the increase in DOPA decarboxylase (DDC) and monoamine oxidase (MAO) activities. In decentralized superior cervical ganglia potassium depolarization failed to produce the specific TH and DBH induction although a small increase in DDC activity persisted. Carbamylcholine, acetylcholine and nicotine at concentrations of 10(-4) M elicited a selective induction of TH and DBH both in intact and decentralized ganglia via nicotinic receptor stimulation. Bethanechol, predominantly stimulating muscarinic receptors had no significant effect on TH activity. A 4 h pulse of 10(-4) M carbamylcholine produced optimal induction of DBH and TH 24 h and 48 h later respectively. Longer exposure to carbamylcholine resulted in a significantly smaller rise in TH activity.

Acetylcholine↗
PubMed1984

Catecholamine-related enzymes and the biopterin cofactor in Parkinson's disease and related extrapyramidal diseases.

In parkinsonian brain, TH and the BP cofactor, as well as DBH and PNMT with phenylethanolamine as substrate, are decreased. However, decrease in AADC with L-DOPA as substrate was not statistically significant. TH activity has also been shown to be decreased in striatonigral degeneration and Shy-Drager syndrome. TH reduction only in striatum but not in substantia nigra was found in a case of juvenile Parkinson's disease. Changes in AADC with L-DOPA or L-5-HTP as substrates varied in parkinsonian brains. PNMT with norepinephrine as substrate was also significantly decreased in parkinsonian brains. After administration of tyrosine to mice, the BP concentration was increased in striatum, adrenals, and serum. Mean BP concentration in serum of parkinsonian patients was slightly but significantly lower than that in controls. The serum BP increased three- to sevenfold in response to an oral tyrosine load in controls, whereas there was no increase or only a minor one (less than threefold) in parkinsonian patients. Our present results indicate that all catecholamine-synthesizing enzymes and BP synthesis may be impaired in Parkinson's disease.

Adult↗