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PubMed2005

Velo-cardio-facial syndrome.

PURPOSE OF REVIEW: Velo-cardio-facial syndrome has emerged from obscurity to become one of the most researched disorders this past decade. It is one of the most common genetic syndromes in humans, the most common contiguous gene syndrome in humans, the most common syndrome of cleft palate, and the most common syndrome of conotruncal heart malformations. Velo-cardio-facial syndrome has an expansive phenotype, a factor reflected in the wide range of studies that cover both clinical features and molecular genetics. In this review, we cover multiple areas of research during the past year, including psychiatric disorders, neuroimaging, and the delineation of clinical features. RECENT FINDINGS: The identification of candidate genes for heart anomalies, mental illness, and other clinical phenotypes has been reported in the past year with a focus on TBX1 for cardiac and craniofacial phenotypes and COMT and PRODH for psychiatric disorders. The expansive phenotype of velo-cardio-facial syndrome continues to grow with new behavioral and structural anomalies reported. Treatment issues are beginning to draw attention, although most authors continue to focus on diagnostic issues. SUMMARY: Its high population prevalence, estimated to be as common as 1:2000 has sparked a large amount of research, as has the model the syndrome serves for identifying the causes of mental illness and learning disabilities, but it is obvious that more information is needed. Intensive scrutiny of velo-cardio-facial syndrome will undoubtedly continue for many years to come with the hope that researchers will turn more of their attention to treatment and treatment outcomes.

Catechol O-Methyltransferase↗

PubMedDate not supplied

Levodopa infusion therapy in Parkinson disease: state of the art in 2004.

Orally administered levodopa, in combination with a decarboxylase inhibitor, is the gold standard therapy for Parkinson disease (PD). The problems in management of motor fluctuations in the advanced stages of the disorder are due to the close relationship between plasma levodopa levels and availability of dopamine at striatal receptor sites. The fluctuating levodopa concentrations are mainly explained by the fact that levodopa absorption only occurs in the proximal small intestine. The patient's motor function thus depends on gastric emptying, which is erratic and may even be delayed in PD. Oral therapy with sustained-release formulations and COMT inhibitors have not solved the problems satisfactorily. Therefore, infusions of levodopa by intravenous and enteral (duodenal/jejunal) routes of administration have been studied. In this review of the literature on clinically relevant levodopa infusion studies, it is shown that improvements regarding fluctuations in both plasma levodopa levels and motor performance have been repeatedly reported. The results acquired so far suggest that levodopa infusion is a safe and efficacious therapy. Recent drug delivery development and long-term studies have shown that infusion is a clinically feasible alternative to treat advanced PD.

Adult↗

PubMed2004

Hippocampal gene expression profiling across eight mouse inbred strains: towards understanding the molecular basis for behaviour.

Mouse inbred strains differ in many aspects of their phenotypes, and it is known that gene expression does so too. This gives us an opportunity to isolate the genetic aspect of variation in expression and compare it to other phenotypic variables. We have investigated these issues using an eight-strain expression profile comparison with four replicates per strain on Affymetrix MGU74av2 GeneChips focusing on one well-defined brain tissue (the hippocampus). We identified substantial strain-specific variation in hippocampal gene expression, with more than two hundred genes showing strain differences by a very conservative criterion. Many such genetically driven differences in gene expression are likely to result in functional differences including differences in behaviour. A large panel of inbred strains could be used to identify genes functionally involved in particular phenotypes, similar to genetic correlation. The genetic correlation between expression profiles and function is potentially very powerful, especially given the current large-scale generation of phenotypic data on multiple strains (the Mouse Phenome Project). As an example, the strongest genetic correlation between more than 200 probe sets showing significant differences among our eight inbred strains and a ranking of these strains by aggression phenotype was found for Comt, a gene known to be involved in aggression.

Analysis of Variance↗

PubMed2005

Genetic variability and clinical efficacy of morphine.

The individual variability of opioid pharmacology suggests that the patients' genetic disposition influences the response to opioids. Given the complexity of morphine pharmacology, variability may be caused by several genes. We review data which shows that variability in genes coding the enzyme metabolizing morphine (UGT2B7 gene), mu-opioid receptors (OPRM gene) and blood-brain barrier (BBB) transport of morphine by multidrug resistance transporters (MDR1 gene) influences the clinical efficacy of morphine. Furthermore, variability in an enzyme degrading catecholamines (COMT gene) alters the efficacy of morphine demonstrating that genetic variability in non-opioid systems may indirectly influence the clinical efficacy from morphine. Thus, results obtained so far strongly argue that opioid efficacy is partly related to inborn properties caused by genetic variability.

Catechol O-Methyltransferase↗

PubMed1999

The effect of tolcapone on the pharmacokinetics of benserazide.

This study investigated the potential interaction between tolcapone, a catechol-O-methyltransferase (COMT) inhibitor, and the decarboxylase inhibitor, benserazide. In an open-labelled six-week study, patients with Parkinson's disease (PD), treated with levodopa/benserazide, were given tolcapone at 200 mg t.i.d. Blood samples for analysis of benserazide, its main active metabolite, trihydroxybenzylhydrazine, levodopa and 3-O- methyldopa (3-OMD) were collected immediately before and repeatedly after the first drug intake of the day at baseline and after 1-2 and 6 weeks of treatment. Furthermore, animal experiments were performed to determine the levels of benserazide and trihydroxybenzylhydrazine at doses for which safety had previously been established. It was shown that tolcapone can cause an increase in benserazide plasma concentrations and that this effect is dependent on the benserazide dose. When tolcapone was combined with 25 mg benserazide the elevation was small. Although the increase was more pronounced when tolcapone was combined with 50 mg benserazide, the levels were still substantially lower than concentrations causing toxicity in animals. The safety margin derived from this study, together with the absence of any organic toxic effects in clinical trials, show that the observed interaction between tolcapone and benserazide does not represent a safety concern for PD patients treated with this combination.

Aged↗

PubMed2004

Delayed administration may improve entacapone effects in parkinsonian patients non-responding to the drug.

BACKGROUND: Entacapone is a COMT inhibitor used in Parkinson's disease (PD) patients, as an adjunctive therapy to L-dopa in order to prolong its bioavailability and thus its clinical effect. However, previous studies reported entacapone-induced L-dopa to have lower C(max) and delayed t(max) values, coupled with a delayed onset of the clinical effect, possibly suggesting an interference between the two drugs. The aim of our study was to evaluate whether a delayed entacapone administration in association with standard L-dopa/carbidopa, may in some subjects improve the entacapone effects on L-dopa AUC and thus on the clinical 'on time' duration. METHODS: Twenty-eight idiopathic advanced PD patients were blindly evaluated in three different test days, following administration of carbidopa/L-dopa or carbidopa/L-dopa plus co-administered entacapone or plus entacapone administered with 30 min of delay. RESULTS: The AUC, the 'on time' and UPDRS score of the whole group were improved by both modalities of entacapone administration. An ex post analysis showed that the delayed entacapone administration produced a significant improvement in a subgroup of 10 non-responding patients to the co-administration. CONCLUSION: We suggest that the delayed administration should be attempted in the subjects not improved by entacapone co-administration.

Aged↗

PubMed1982

A comparison of 2-hydroxyestradiol and U-0521 (3'4'-dihydroxy-2-methylpropiophenone, Upjohn) as in situ and in vitro inhibitors of tyrosine hydroxylase.

Feedback inhibition of tyrosine hydroxylase by catechols was evaluated using in situ and in vitro enzyme assays. The three catechol compounds used were norepinephrine, 2-hydroxyestradiol, and 3'4'-dihydroxy-2-methylpropiophenone (U-0521, Upjohn); representing endogenous catecholamines, catechol estrogens, and a synthetic catechol, respectively. The in situ experiments were performed with dissociated retinal cells from rats and with stationary phase adrenergic-like neuroblastoma cells (N1E-115). The catechol estrogen, 2-hydroxyestradiol, resembled the endogenous catecholamine in its potency to inhibit in vitro and in situ tyrosine hydroxylations with IC50 values of 10 microM in vitro and 100 microM in situ. The drug U-0521, which has been used as an inhibitor of catechol-O-methyltransferase (COMT), was also found to be an inhibitor of tyrosine hydroxylase. Further, it was shown to be more potent than the natural catechols, both in vitro and in situ, with IC50 values of 30--600 nM.

Adrenal Glands↗

PubMed1981

Regional distribution of methionine adenosyltransferase in rat brain as measured by a rapid radiochemical method.

The distribution of methionine adenosyltransferase (MAT) in the CNS of the rat was studied by use of a rapid, sensitive and specific radiochemical method. The S-adenosyl-[methyl-14C]L-methionine ([14C]SAM) generated by adenosyl transfer from ATP to [methyl-14C]L-methionine is quantitated by use of a SAM-consuming transmethylation reaction. Catechol O-methyltransferase (COMT), prepared from rat liver, transfers the methyl-14C group of SAM to 3,4-dihydroxybenzoic acid. The 14C-labelled methylation products, vanillic acid and isovanillic acid, are separated from unreacted methionine by solvent extraction and quantitated by liquid scintillation counting. Compared to other methods of MAT determination, which include separation of generated SAM from methionine by ion-exchange chromatography, the assay described exhibited the same high degree of specificity and sensitivity but proved to be less time consuming. MAT activity was found to be uniformly distributed between various brain regions and the pituitary gland of adult male rats. In the pineal gland the enzyme activity is about tenfold higher.

Amygdala↗

PubMed1984

Formation and clearance of norepinephrine glycol metabolites in mouse brain.

To determine the degree of conversion of 3,4-dihydroxyphenylethyleneglycol (DHPG) to 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and the amount of DHPG eliminated unchanged from the brain, we have examined the kinetics of formation and disappearance of mouse brain MHPG and DHPG following clorgyline (10 mg/kg, i.p.) and/or tropolone (75 mg/kg, i.p.) treatment. During the first 10 min after tropolone, brain DHPG levels accumulated linearly at a rate of 1,300 pmol/g/h, whereas MHPG disappeared exponentially at a rate of 411 pmol/g/h. Following clorgyline administration, brain DHPG declined exponentially at a rate of 1,240 pmol/g/h. In contrast, the elimination of MHPG became a first-order process only when catechol-O-methyltransferase (COMT) was also inhibited in addition to monoamine oxidase. Thus, combined clorgyline and tropolone treatment resulted in an exponential decline of MHPG levels at a rate of 524 pmol/g/h, whereas DHPG levels were slightly but significantly elevated compared to control values. When the animals were treated with pargyline (75 mg/kg, i.p.) in combination with clorgyline and tropolone, brain DHPG and MHPG disappeared at rates of 40 and 660 pmol/g/h, respectively. The above observations suggest that mouse brain DHPG is cleared primarily through O-methylation with minimal direct elimination from brain. Assuming the disposition and clearance of norepinephrine metabolites are similar in mouse and human brain, peripherally measured DHPG in humans is likely derived principally from extracerebral sources and reflects peripheral sympathetic function.

Animals↗

PubMed1993

Dopamine formation, from its immediate precursor 3,4-dihydroxyphenylalanine, along the rat digestive tract.

The formation of dopamine, from L-3,4-dihydroxyphenylalanine (L-dopa), in fragments of non-glandular and glandular stomach, duodenum, jejunum, ileum and proximal and distal colon of the rat was examined. The deamination of newly-formed dopamine into 3,4-dihydroxyphenylacetic acid (dopac) was also studied. The synthesis of dopamine in tissues incubated with 500 microM L-dopa for 20 min in conditions of catechol-O-methyltransferase (Comt) inhibition was found to be in the duodenum, jejunum and ileum 2-fold that in the proximal colon, 6-fold that in the glandular stomach and 120-fold that in the non-glandular stomach and distal colon. The formation of dopac in these tissues followed the pattern of amine formation. In the jejunum, the formation of dopamine and dopac was found to be dependent on the concentration of L-dopa (50 to 5000 microM) used. In another set of experiments, it was found that the formation of dopamine in jejunal segments loaded with increasing concentrations of L-dopa (50, 100 and 500 microM) was a time-dependent process. The rate constant (k) of formation of dopamine as a function of time was found to be similar (0.050 +/- 0.005) with either concentration of L-dopa; the rate constant of dopac formation in these experiments was, in contrast, found to be greater at the highest concentrations of L-dopa (100 and 500 microM). Aromatic L-amino acid decarboxylase (Aaad) activity determined in homogenates of the jejunal mucosa was found to be twice that observed in homogenates of the remaining jejunal wall (muscular).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1971

3,4-dihydroxyphenylacetic acid and 4-hydroxy-3-methoxyphenylacetic acid in the mouse striatum: a reflection of intra- and extra-neuronal metabolism of dopamine?

1. The administration of probenecid to mice increased the concentration of 4-hydroxy-3-methoxyphenylacetic acid (HVA) in the striatum, but did not raise the concentration of 3,4-dihydroxyphenylacetic acid (DOPAC).2. After drug treatments which normally increase the concentration of HVA several-fold, inhibition of catechol-O-methyltransferase (COMT) by tropolone greatly reduced the concentration of HVA but resulted in only a small increase in the concentration of DOPAC in the striatum of the mouse.3. These results indicate that HVA and DOPAC do not occur at the same location in the tissue of the striatum and that DOPAC is not normally metabolized to HVA to any great extent in this tissue.4. When mice were treated with reserpine, which is thought to prevent the intraneuronal storage of dopamine, there was an increase in the striatal concentration of DOPAC which preceded an increase in the concentration of HVA. Since non-cholinergic nerve endings of rat brain contain mitochondria and show monoamine oxidase activity, this result suggests that DOPAC is formed intraneuronally.5. It is concluded that the DOPAC in the striatum represents intraneuronal metabolism of dopamine and that only the HVA which is sensitive to the action of probenecid represents entirely extraneuronal metabolism of this amine. Some of the HVA is not sensitive to the action of probenecid. This suggests that part of the metabolism of dopamine involved both locations.6. A group of drugs which are chemically related to amphetamine were tested for their effects on the concentrations of DOPAC and HVA in the striatum. It is suggested that D-amphetamine, 2-aminotetralin and 1,2,3,4-tetrahydroisoquinoline reduced the intraneuronal metabolism of dopamine whereas adamantanamine did not.

Amantadine↗

PubMed1982

Desensitization by noradrenaline of responses to stimulation of pre- and postsynaptic adrenoceptors.

1 The effect of exposing isolated preparations of rat aortic strip, rat atria and mouse vas deferens to perfusions of Krebs solution containing various concentrations of noradrenaline on their sensitivity to the drug has been determined.2 The responses evoked by stimulation of postsynaptic adrenoceptors in all the tissues and presynaptic alpha-adrenoceptors in the mouse vas deferens were diminished by the perfusion of noradrenaline through the organ bath for 30 min.3 The concentration of noradrenaline required to produce desensitization was higher in the mouse vas deferens than in the other tissues and more was required to desensitize the chronotropic responses than the inotropic responses in rat isolated atria.4 The inclusion of cocaine (10(-5) M) in the bathing solution to block uptake(1) increased the sensitivity of most tissues to noradrenaline. With the possible exception of the response to stimulation of presynaptic receptors in the mouse vas deferens, desensitization was somewhat increased in its presence.5 When uptake(2) was blocked by oestradiol (10(-5) M), it was not possible to desensitize the contractor responses of the aortic strip and vas deferens to exogenous noradrenaline, nor the inotropic response of the atria to the drug. However, oestradiol failed to block the desensitization of chronotropic responses and responses to stimulation of presynaptic receptors in the vas deferens.6 Blockade of monoamine oxidase (MAO) with iproniazid (7.2 x 10(-4) M) or with pargyline (5 x 10(-4) M) did not affect the desensitization process in the aortic strip.7 Blockade of catechol-O-methyltransferase (COMT) with U-0521 (5.3 x 10(-5) M) greatly increased desensitization in the aortic strip and desensitization of inotropic responses in the atria. It had no effect on desensitization of chronotropic responses. Its effect on responses in the mouse vas deferens was not determined.8 The perfusion of methoxamine at concentrations about 1000 times higher than those of noradrenaline also produced desensitization in the aortic strip.9 The desensitization of presynaptic receptors in the mouse vas deferens was shown to be specific and that of the responses to postsynaptic receptor stimulation to be non-specific.10 It is concluded that responses to adrenoceptor stimulation may be desensitized by accumulation of noradrenaline inside the cells bearing the receptors and that the desensitization is caused by noradrenaline itself not by a metabolite. Desensitization may also be caused without accumulation of noradrenaline in uptake(2) and for some receptors these may not be alternative mechanisms.

Animals↗

PubMed1983

Temperature-induced changes in dissociation constants (KA) of agonists at cardiac beta-adrenoceptors determined by use of the irreversible antagonist Ro 03-7894.

The positive inotropic responses of guinea-pig left atria and papillary muscles and positive chronotropic responses of right atria to sympathomimetic amines were examined at 38 degrees and 30 degrees C. At the lower temperature, supersensitivity to orciprenaline and isoprenaline was exhibited as shifts of the dose-response curves to the left and significant reductions in EC50 values. This supersensitivity could not be attributed to reduced metabolism since the experiments were performed in the presence of metanephrine (10(-5)M) and U-0521 (3',4'-dihydroxy-2-methylpropiophenone) (10(-4)M) as inhibitors of extraneuronal uptake and catechol-O-methyltransferase (COMT) respectively, and the agonists are not susceptible to neuronal uptake. After incubation of the tissues with Ro 03-7894 (1-(5-chloracetylaminobenzfuran-2-yl)-2-isopropylaminoethanol), followed by its prolonged washout (greater than 2h), the maximum responses to isoprenaline and orciprenaline were depressed, confirming the apparently irreversible beta-adrenoceptor antagonism. Dissociation constants (KA) for isoprenaline and orciprenaline were determined from the equiactive concentrations obtained before (A) and after (A') incubation with Ro 03-7894, plotted as 1/A against 1/A' (KA = (slope-1)/intercept). KA values were the same for orciprenaline in the three cardiac preparations and for isoprenaline in the atria. This applied at 38 degrees and 30 degrees C and indicates that the beta-adrenoceptors mediating the inotropic and chronotropic responses of the guinea-pig heart do not differ. The KA values of both agonists were, however, consistently and significantly lower at 30 degrees than at 38 degrees C, indicating an increase in affinity. 8 It is concluded that hypothermia-induced supersensitivity of cardiac tissue to sympathomimetic amines is associated with an increase in their affinity for the B-adrenoceptors.

Adrenergic beta-Agonists↗

PubMed1995

Assessment of renal dopaminergic system activity during cyclosporine A administration in the rat.

1. Administration of cyclosporine A (CsA; 50 mg kg-1 day-1, s.c.) for 14 days produced an increase in both systolic (SBP) and diastolic (DBP) blood pressure by 60 and 25 mmHg, respectively. The urinary excretion of dopamine, DOPAC and HVA was reduced from day 5-6 of CsA administration onwards (dopamine from 19 to 46%, DOPAC from 16 to 48%; HVA from 18 to 42%). In vehicle-treated rats, the urinary excretion of dopamine and DOPAC increased (from 7 to 60%) from day 5 onwards; by contrast, the urinary excretion of HVA was reduced (from 27 to 60%) during the second week. 2. No significant difference was observed between the Vmax and Km values of renal aromatic L-amino acid decarboxylase (AAAD) in rats treated with CsA for 7 and 14 days or with vehicle. 3. Km and Vmax of monoamine oxidase types A and B did not differ significantly between rats treated with CsA for 7 and 14 days or with vehicle. 4. Maximal catechol-O-methyltransferase activity (Vmax) in homogenates of renal tissues obtained from rats treated with CsA for 7 or 14 days was significantly higher than that in vehicle-treated rats; Km (22.3 +/- 1.5 microM) values for COMT did not differ between the three groups of rats. 5. The accumulation of newly-formed dopamine and DOPAC in cortical tissues of rats treated with CsA for 14 days was three to four times higher than in controls. The outflow of both dopamine and DOPAC declined progressively with time and reflected the amine and amine metabolite tissue contents. No significant difference was observed between the DOPAC/dopamine ratios in the perifusate of renal tissues obtained from CsA- and vehicle-treated rats. In addition, no significant differences were observed in k values or in the slope of decline of both DA and DOPAC between experiments performed with CsA and vehicle-treated animals. 6. The Vmax for the saturable component of L-3,4-dihydroxyphenylalanine (L-DOPA) uptake in renal tubules from rats treated with CsA was twice that of vehicle-treated animals. Km in CsA- and vehicle-treated rats did not differ. 7. The decrease in the urinary excretion of sodium and an increase in blood pressure during CsA treatment was accompanied by a reduction in daily urinary excretion of dopamine. This appears to result from a reduction in the amount of L-DOPA made available to the kidney and does not involve changes in tubular AAAD, the availability of dopamine to leave the renal cells and dopamine metabolism. The enhanced ability of the renal tissues of CsA-treated animals to synthesize dopamine, when exogenous L-DOPA is provided, results from an enhanced activity of the uptake process of L-DOPA in renal tubular cells.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1996

Minor effect of tolcapone, a catechol-O-methyltransferase inhibitor, on extracellular dopamine levels modified by amphetamine or pargyline: a microdialysis study in anaesthetized rats.

In vivo microdialysis was used to examine the effects of tolcapone (30 mg/kg) on dopamine metabolism in amphetamine (5 mg/kg) and pargyline (75 mg/kg) treated rats. Amphetamine- or pargyline-induced decreases in the extracellular dihydroxyphenyl acetic acid (DOPAC) levels were counteracted by additional tolcapone. Tolcapone also decreased homovanillic acid effluxes below those caused by amphetamine or pargyline. However, dopamine effluxes were not further enhanced by additional tolcapone. These results show that central metabolism of dopamine can be modulated by catechol-O-methyltransferase (COMT) inhibition also without exogenous L-DOPA. However, extracellular dopamine levels are not easily increased.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1994

Effects of chronic melatonin administration on adrenal medulla catecholamine metabolism in adult male golden hamsters.

The role of melatonin on adrenal medullary function was evaluated in adult golden (Syrian) hamsters injected daily at either 0800 or 1600 with melatonin (25 micrograms/hamster) or vehicle (0.1% ethanol in saline). Sixty days after initiation of treatment and 16 or 24 hr after the last injection of melatonin, animals were killed by decapitation and blood and tissue collected. Plasma prolactin levels were reduced by chronic administration of melatonin only when animals were treated at 1600. Tyrosine hydroxylase (TH) activity in the adrenal medulla was not changed by either morning or afternoon administration of melatonin. Phenylethanolamine-N-methyl transferase (PNMT) was changed by afternoon administration of melatonin. Morning and afternoon melatonin injections led to the reduction of both adrenal monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) activities although the afternoon injections led to a greater magnitude of change. Norepinephrine and epinephrine contents were significantly reduced by morning melatonin administration but were not changed by afternoon administration of the hormone. These data suggest that melatonin has direct and possibly indirect effects on adrenal medullary function in the hamster. However, further studies will be required to characterize the effects of melatonin on catecholamine synthesis and release and the physiological significance of these effects.

Adrenal Medulla↗

PubMed2006

Molecular genetics of bipolar disorder.

Bipolar disorder (BPD) is an often devastating illness characterized by extreme mood dysregulation. Although family, twin and adoption studies consistently indicate a strong genetic component, specific genes that contribute to the illness remain unclear. This study gives an overview of linkage studies of BPD, concluding that the regions with the best evidence for linkage include areas on chromosomes 2p, 4p, 4q, 6q, 8q, 11p, 12q, 13q, 16p, 16q, 18p, 18q, 21q, 22q and Xq. Association studies are summarized, which support a possible role for numerous candidate genes in BPD including COMT, DAT, HTR4, DRD4, DRD2, HTR2A, 5-HTT, the G72/G30 complex, DISC1, P2RX7, MAOA and BDNF. Animal models related to bipolar illness are also reviewed, with special attention paid to those with clear genetic implications. We conclude with suggestions for strategies that may help clarify the genetic bases of this complex illness.

Animals↗

PubMed1980

Barrier mechanisms for neutrotransmitter monoamines in the choroid plexus.

Studies were performed on choroid plexuses from mouse and rat. The plexus tissue, sympathectomized to avoid interference from adrenergic nerves, is able to accumulate L-DOPA as well as NA and 5-HT against a concentration gradient. Within the plexus tissue these compounds are metabolized by aromatic L-amino acid decarboxylase, MAO and COMT, whose activities were determined radiometrically. On the basis of this and the fate of systemically administered L-DOPA and DA studied by fluorescence histochemistry it is suggested that the epithelium of the choroid plexus provides not only a structural but also an enzymatic barrier for transmitter amines. The enzymatic barrier for amine precursors is considerably less sufficient at this blood-CSF interphase. The trapping of monoamines resembles the enzymatic barrier present in the endothelial cells and pericytes at the microvascular level of the blood-brain interphase.

Animals↗