Oxidative Maturation and Structural Characterization of Prenylated FMN Binding by UbiD, a Decarboxylase Involved in Bacterial Ubiquinone Biosynthesis.

The activity of the reversible decarboxylase enzyme Fdc1 is dependent on prenylated FMN (prFMN), a recently discovered cofactor. The oxidized prFMN supports a 1,3-dipolar cycloaddition mechanism that underpins reversible decarboxylation. Fdc1 is a distinct member of the UbiD family of enzymes, with the canonical UbiD catalyzing the (de)carboxylation of para-hydroxybenzoic acid-type substrates. Here we show that the Escherichia coli UbiD enzyme, which is implicated in ubiquinone biosynthesis, cannot be isolated in an active holoenzyme form despite the fact active holoFdc1 is readily obtained. Formation of holoUbiD requires reconstitution in vitro of the apoUbiD with reduced prFMN. Furthermore, although the Fdc1 apoenzyme can be readily reconstituted and activated, in vitro oxidation to the mature prFMN cofactor stalls at formation of a radical prFMN species in holoUbiD. Further oxidative maturation in vitro occurs only at alkaline pH, suggesting a proton-coupled electron transfer precedes formation of the fully oxidized prFMN. Crystal structures of holoUbiD reveal a relatively open active site potentially occluded from solvent through domain motion. The presence of a prFMN sulfite-adduct in one of the UbiD crystal structures confirms oxidative maturation does occur at ambient pH on a slow time scale. Activity could not be detected for a range of putative para-hydroxybenzoic acid substrates tested. However, the lack of an obvious hydrophobic binding pocket for the octaprenyl tail of the proposed ubiquinone precursor substrate does suggest UbiD might act on a non-prenylated precursor. Our data reveals an unexpected variation occurs in domain mobility, prFMN binding, and maturation by the UbiD enzyme family.

Different changes in slope between the medial and lateral tibial plateau after open-wedge high tibial osteotomy.

PURPOSE: In contrast to radiographic measurements, MRI provides multiple slices of the knee joint in the sagittal plane, making it possible to assess the medial and lateral tibial slope separately. The purpose of this study is to investigate the effect of medial open-wedge high tibial osteotomy (MOWHTO) on bony and meniscal slope in the medial and lateral tibiofemoral compartments. It was hypothesised that greater changes on the medial tibial plateau would be observed compared with the lateral one. METHODS: A retrospective analysis of prospectively collected data was performed on pre- and post-operative MRIs from 21 patients (17 men and 4 women; age 52 ± 9 years). Inclusion criteria were varus alignment, medial compartment osteoarthritis and election for a primary MOWHTO. Each patient had a preoperative and a post-operative high-resolution MRI (3Tesla, Magnetom Trio, Siemens AG) at an average follow-up of 2.1 years. A previously published method was used to measure bony and meniscal slope for each compartment. The difference between pre- and post-operative tibial slope for both compartments was calculated and associated with the amount of frontal correction. RESULTS: There was a significant increase in bony tibial slope in both compartments following MOWHTO. When a change in bony tibial slope was detected in an individual patient, the change was larger in the medial compartment, with the average change also significantly greater (p < 0.01) in the medial compartment (2.4° ± 1.3°) compared with the lateral compartment (0.9° ± 1.1°). There was also a significant increase (p < 0.01) in the lateral tibial meniscal slope of 0.9° ± 1.4°, which was equivalent to the change in the bony lateral slope. The amount of frontal correction was not significantly associated with the amount of change in slope. CONCLUSIONS: The results suggest that the modification of the bony slope is larger in the medial compartment after MOWHTO, which is likely related to the location of the hinge on the lateral tibial cortex. These findings suggest that consideration of the medial and lateral tibial slope intra-operatively could be important to identify the optimal location of the hinge. However, further studies are required before recommending any modification to the surgical technique, as the potential clinical consequences of tibial slope alterations remain unknown. LEVEL OF EVIDENCE: IV.

Emotional scene processing in biotypes of psychosis.

Social-emotional deficits in psychosis may be indexed by deviations in emotional scene processing, but event-related potential (ERP) studies indicate such deviations may not map cleanly to diagnostic categories. Neurobiologically defined psychosis subgroups offer an alternative that may better capture neurophysiological correlates of social-emotional deficits. The current study investigates emotional scene-elicited ERPs in Biotypes of psychosis in a large (N = 622), well-characterized sample. Electroencephalography was recorded in healthy persons (N = 129), Biotype-1 (N = 195), Biotype-2 (N = 131), and Biotype-3 (N = 167) psychosis cases. ERPs were measured from posterior and centroparietal scalp locations. Neural responses to emotional scenes were compared between healthy and psychosis groups. Multivariate group discrimination analyses resulted in two composite variates that differentiated groups. The first variate displayed large differences between low-cognition (Biotype-1, Biotype-2) and intact-cognition groups (Biotype-3, healthy persons). The second indicated a small-to-moderate distinction of Biotypes-2 and -3 from Biotype-1 and healthy persons. Two multivariate correlations were identified indicating associations between 1) self-reported emotional experience and generalized cognition and 2) socio-occupational functioning and late-stage emotional processing. Psychosis Biotypes displayed emotional processing deficits not apparent in DSM psychosis subgroups. Future translational research may benefit from exploring emotional scene processing in such neurobiologically-defined psychosis groups.

Isolated rupture of the lateral collateral ligament during yoga practice: a case report.

We report a case of isolated rupture of the lateral collateral ligament (LCL) of the knee while attempting to place the left foot behind the head during yoga practice. The 34-year-old man had discomfort of the lateral aspect of the knee particularly with varus strain. A magnetic resonance image revealed rupture of the LCL at the insertion onto the fibula. The patient had grade-II laxity of the LCL and was treated non-operatively. At the 12-month follow-up, grade-I laxity of the LCL remained clinically evident, but function was not impaired.

Complex regional pain syndrome complicating total knee arthroplasty.

PURPOSE: To compare the long-term outcome of patients diagnosed with complex regional pain syndrome-type 1 (CRPS-1) after total knee arthroplasty (TKA) with those of uncomplicated TKA knees and preoperative osteoarthritic knees. METHODS: Medical records of 1280 patients who underwent TKA for osteoarthritis were retrospectively reviewed; 8 were diagnosed as having symptoms and signs consistent with CRPS after TKA. Patients with primary inflammatory arthritis, signs of component loosening, malpositioning, or of infected arthroplasty were excluded. No patient had signs of CRPS prior to operative intervention. The 8 patients were compared with 2 groups of age- and sex-matched controls: uncomplicated TKA knees and preoperative osteoarthritic knees. Patients were followed up for a mean of 54 (range, 13-111) months and their range of movement, Western Ontario and McMaster Universities Osteoarthritis Index, SF-36 questionnaire scores, and Knee Society scores were assessed and compared. RESULTS: After appropriate treatment, most CRPS complicated patients had similar scores on SF-36, Western Ontario and McMaster Universities Osteoarthritis Index, and Knee Society scores when compared with uncomplicated TKA patients. Scores for CRPS complicated patients were significantly improved when compared with preoperative osteoarthritic patients. The incidence of CRPS after TKA was 0.7%. CONCLUSION: When managed early, patients complicated with CRPS after TKA have a similar prognosis to patients with uncomplicated TKA.

Patient outcomes using Wii-enhanced rehabilitation after total knee replacement - the TKR-POWER study.

BACKGROUND: Home-based rehabilitation following total knee replacement surgery can be as effective as clinic-based or in-patient rehabilitation. The use of the Nintendo Wii has been postulated as a novel rehabilitation tool that adds an additional focus on balance and proprioception into the recovery protocol. The aim of the proposed clinical trial is to investigate the effectiveness of this novel rehabilitation tool, used at home for three months after total knee replacement surgery and to assess any lasting improvements in functional outcome at one year. METHODS/DESIGN: This will be a randomised controlled trial of 128 patients undergoing primary total knee replacement. The participants will be recruited preoperatively from three surgeons at a single centre. There will be no change to the usual care provided until 6 weeks after the operation. Then participants will be randomised to either the Wii-Fit group or usual rehabilitative care group. Outcomes will be assessed preoperatively, a 6-week post surgery baseline and then at 18 weeks, 6 months and 1 year. The primary outcome is the change in self-reported WOMAC total score from week 6 to 18 weeks. Secondary outcomes include objective measures of strength, function and satisfaction scores. DISCUSSION: The results of this clinical trial will be directly relevant for implementation into clinical practice. If beneficial, this affordable technology could be used by many patients to rehabilitate at home. Not only could it optimize the outcomes from their total knee replacement surgery but decrease the need for clinic-based or outpatient therapy for the majority. TRIAL REGISTRATION: (ACTRN12611000291987).

Metastatic carcinoma of prostate.

A case is reported of a seventy-seven-year-old man with an unusual soft tissue metastasis in the pelvis from carcinoma of the prostate.

Endometrial carcinoma of prostatic utricle with osseous metastases.

Endometrial carcinoma of the prostatic utricle is a rare pupillary prostatic tumor arising in the region of the prostatic urethra and verumontanum. Since the first description by Melicow and Pachter in 1967, 8 additional cases have been reported. This case is the tenth reported, and the first in which metastases to bone have been proved by biopsy. Transurethral resection of the tumor with postoperative radiation therapy to the prostatic region and metastases has resulted in clinical improvement. The importance of accurate diagnosis of this neoplasm is emphasized to avoid unnecessary delay in the appropriate choice of therapeutic modalities.

The morpholino-acetic acid analogue Sch 50911 is a selective GABA(B) receptor antagonist in rat neocortical slices.

The pharmacological properties of (+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid (Sch 50911) were evaluated on GABA(B) receptors in rat neocortical slices. The GABA(B) receptor agonist, baclofen, produced a concentration-dependent depression of the frequency of spontaneous discharges in slices maintained in Mg2+-free Krebs medium with an EC50 of 6 microM, reversibly antagonised by Sch 50911 (5, 10 and 25 microM) with an apparent pA2 of 6.0 +/- 0.1. The (-) enantiomer Sch 50910 (500 microM) and the racemic des-methyl analogue Sch 48588 (500 microM) were inactive. In slices preloaded with [3H]GABA, Sch 50911 antagonised GABA(B) autoreceptors, increasing the electrically-stimulated 3H overflow in a concentration-dependent manner, with an IC50 of 3 microM. The maximal effect (148 +/- 10.5%) was found at 10 microM, but at 50 microM the response was reduced to 67 +/- 19%. In contrast, evoked release was unaffected by Sch 50910 (100 microM) whilst Sch 48588 at 100 microM increased the overflow by 51.3 +/- 11.6%. In summary, Sch 50911 is a relatively potent antagonist of considerable potential in studies of GABA(B) receptor function.

Comparative activities of the enantiomeric GABA(B) receptor agonists CGP 44532 and 44533 in central and peripheral tissues.

In neocortical slices maintained in Mg(2+)-free Krebs medium, the gamma-aminobutyric acid (GABA(B)) receptor agonists baclofen, (3-amino-2(S)-hydroxypropyl)methylphosphinic acid (CGP 44532), and its (R)-enantiomer CGP 44533 depressed the frequency of spontaneous discharges in a concentration-dependent manner (EC(50)=10, 6.5, and 50 microM, respectively). These effects were reversibly antagonised by the GABA(B) receptor antagonist (+)-(S)-5,5 dimethylmorpholinyl-2-acetic acid (Sch 50911) (3, 10, and 30 microM) (average pA(2) value=6.0+/-0.2). In neocortical wedges, baclofen, CGP 44532 and CGP 44533 elicited concentration-dependent hyperpolarisations (the EC(50)s were 14, 7.5 and 16 microM, respectively) sensitive to Sch 50911 (1, 5, 10 microM) (average pA(2) value=6.0+/-0.1), whilst they also depressed ileal electrically elicited cholinergic twitch contractions (EC(50)=11, 7, and 50 microM) that were antagonised by Sch 50911 (average pA(2) value=6.0+/-0.1). In electrically stimulated brain slices preloaded with [3H]GABA, baclofen, CGP 44532 and CGP 44533 decreased [3H]GABA release (IC(50)=5, 0.45, and 10 microM); this effect was reversed by Sch 50911 (50 microM). It is concluded that CGP 44532 is a far more potent agonist at GABA(B) autoreceptors than at central or peripheral heteroreceptors.

CGP 36216 is a selective antagonist at GABA(B) presynaptic receptors in rat brain.

In rat neocortical preparations maintained in Mg(2+)-free Krebs medium, baclofen depressed the frequency of spontaneous discharges in a concentration-dependent manner (EC(50) = 6 microM), sensitive to (3-aminopropyl)ethylphosphinic acid (CGP 36216) (100, 300 and 500 microM) (pA(2) = 3.9 +/- 0.1). By contrast, CGP 36216, up to 1 mM, was ineffective in antagonising baclofen-induced hyperpolarisations, mediated through gamma-aminobutyric acid(B) (GABA(B)) postsynaptic receptors. In electrically stimulated brain slices preloaded with [3H]GABA, CGP 36216 increased [3H]GABA release (IC(50) = 43 microM), which was reversed by baclofen (20 microM). While CGP 36216 is ineffective at GABA(B) postsynaptic receptors, it is appreciably more active at presynaptic receptors.

Pharmacological re-evaluation of a GABA(B) receptor antagonist CGP 47332A in rat brain.

In rat neocortical slices maintained in Mg(2+)-free Krebs medium, the gamma-aminobutyric acid (GABA(B)) receptor agonist baclofen concentration-dependently depressed the frequency of spontaneous discharges (EC(50)=12 microM). This was reversibly antagonised by (R, S)-3-amino-2-hydroxy-propyl-P-n-butyl-phosphinic acid (CGP 47332A) (25, 100, 300 microM) which produced rightwards shifts of the baclofen concentration-response curves (pA(2) value=4.8+/-0.1). In electrically stimulated slices preloaded with [3H]GABA, CGP 47332A increased its release (EC(150)=100 microM) through antagonism of GABA(B) autoreceptors. Although CGP 47332A was some six times weaker on GABA(B) auto- than on heteroreceptors, yet its congener lacking the beta-hydroxy substituent displays equal potency in both binding (IC(50)=38 microM) and GABA(B) autoreceptor functional studies (EC(150)=38 microM) as previously reported [Froestl, W., Mickel, S.J. , Von Sprecher, G., Diel, P.J., Hall, R.G., Maier, L., Strub, D., Melillo, V., Baumann, P.A., Bernasconi, R., Gentsch, C., Hauser, K., Jaekel, J., Karlsson, G., Klebs, K., Maitre, L., Marescaux, C., Pozza, M.F., Schmutz, M., Steinmann, M.W., Van Riezen, H., Vassout, A., Mondadori, C., Olpe, H.R., Waldmeier, P.C., Bittiger, H., Phosphinic acid analogues of GABA: 2. Selective, orally active GABA(B) antagonists. J. Med. Chem. 38 (1995) 3313-3331.].

Antagonism of GABA(B) receptors by morpholino-2-acetic acid derivatives Sch 54679 and Sch 51324 in rat brain.

In rat neocortical slices maintained in Mg2+-free Krebs medium, baclofen depressed the rate of spontaneous discharges in a concentration-dependent manner (EC50 = 4.5 microM). This depression was reversibly antagonised by 5-(S,R)-hydroxymethyl-5-methylmorpholinyl-2-(R,S)-acetic acid (Sch 54679) and 2-(R,S)-5-[spirocyclopentyl]-morpholinyl-acetic acid (Sch 51324) (respective pA2 values of 5.8+/-0.15 and 5.4+/-0.2). In electrically-stimulated slices preloaded with [3H]gamma-aminobutyric acid (GABA), Sch 54679 (EC50 = 3 microM) was 2.3 times more potent than Sch 51324 (EC50 = 7 microM) in increasing [3H]GABA release through antagonism of GABA(B) autoreceptors. These structurally novel analogues may be pharmacologically useful for elucidating GABA(B) receptor functions.

Alcoholic beverage type, recall period effects and functional disability: evidence from the 1983 NHIS.

To replicate a Canada Health Survey (CHS) study that found beer drinking was associated with lower morbidity, National Health Interview Survey (NHIS) data for 19,462 persons were used to examine associations between functional disability and beverage specific ethanol consumption. A functional disability index consisting of morbidity and symptom coping events reported for 2 weeks prior to the NHIS interview was constructed. Alcohol consumption was reported for the same period as disability (coincident recall), or for the 2 weeks prior to the respondent's last drink during the past year (antecedent recall). The analysis controlled for confounders using direct standardization and multiple logistic regression. The results of this investigation were not consistent with the CHS study. Former drinkers and antecedent recall drinkers reported greater disability rates than either non-drinkers or coincident recall drinkers. Antecedent recall drinkers exhibiting a preference for beer and wine were, respectively, 40 and 80 percent more likely to be disabled than non-drinkers. Further, this study found no evidence of a protective effect among any subgroup of drinkers. The finding of a significant interaction between alcohol consumption and alcohol recall period suggests that epidemiologic studies should give greater attention to the classification of drinker groups by proximity of alcohol consumption.

Differential effects of phosphonic analogues of GABA on GABA(B) autoreceptors in rat neocortical slices.

The effects of five phosphonic derivatives of GABA on the release of [3H]-GABA from rat neocortical slices, preloaded with [3H]-GABA, were investigated. Phaclofen and 4-aminobutylphosphonic acid (4-ABPA) increased the overflow of [3H] evoked by electrical stimulation (2 Hz) in a concentration-dependent manner, with similar potencies (phaclofen EC50=0.3 mmol/l, 4-ABPA EC50=0.4 mmol/l). At 3 mmol/l, phaclofen increased the release of [3H]-GABA by 82.6+/-8.6%, and 4-ABPA increased the release by 81.3+/-9.0%. 2-Amino-ethylphosphonic acid (2-AEPA) increased the overflow of [3H] by 46.8+/-10.9% at the highest concentration tested (3 mmol/l). In contrast, the lower phosphonic homologue 3-aminopropylphosphonic acid (3-APPA), and 2-amino-2-(p-chlorophenyl)-ethylphosphonic acid (2-CPEPA), a baclofen analogue, did not modify the stimulated overflow. These results suggest that phaclofen, 4-ABPA and 2-AEPA are antagonists at GABA(B) autoreceptors, the latter being the weakest antagonist, whilst neither 3-APPA nor 2-CPEPA are active at these receptors. Since phaclofen, 4-ABPA and 2-CPEPA are antagonists and 3-APPA a partial agonist/antagonist on GABA(B) heteroreceptors, the lack of effect of 3-APPA and 2-CPEPA on [3H]-GABA release in this study suggests that GABA(B) autoreceptors may be pharmacologically distinct from the heteroreceptors.

Extraneuronal uptake of noradrenaline in rabbit dental pulp: evidence of identity with uptake1.

The extraneuronal removal and disposition of noradrenaline in rabbit dental pulp was examined in view of earlier evidence that the tissue possessed an extraneuronal uptake process resembling neuronal uptake1. Pulp, which had been depleted of sympathetic nerves by homolateral superior cervical ganglionectomy, was incubated in vitro with 3H-noradrenaline in low concentrations (0.025 or 0.18 mumol/l). When the metabolising enzymes (monoamine oxidase, catechol-O-methyl transferase) were active, 3H retention by the denervated pulp, as indicated by the 3H content after the tissue had been washed for 30 min following incubation with 3H-noradrenaline, was less than 3% of that of the innervated pulp. When the enzymes were inhibited, retention rose to approximately 30% of that of the innervated pulp. Analysis of the time course of the 3H efflux indicated that the 3H-noradrenaline in the denervated pulp had accumulated in a single compartment characterised by a t1/2 for efflux of several hours. Accumulation did not occur under Na(+)-free conditions, and was inhibited by desipramine (IC50 less than 0.03 mumol/l) and by substrates of neuronal uptake1. Mean IC50 values of the latter were very similar to those for inhibition of neuronal uptake1 and comprised (in mumol/l): (+)amphetamine (0.29), dopamine (0.31), tyramine (0.39), (-)noradrenaline (0.70), (-)adrenaline (1.50), 5-hydroxytryptamine (20) and bretylium (35). Uptake2 inhibitors were less active (O-methyl isoprenaline, IC50 = 60 mumol/l) than uptake1 inhibitors, or were without inhibitory effects at the concentrations tested (hydrocortisone, 210 mumol/l; 2-methoxy oestrone, 10 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of 6-hydroxydopamine on noradrenaline metabolism linked to neuronal uptake1 and extraneuronal uptake1 in dental pulp in vitro.

The study was undertaken to determine the relative roles of neuronal and extraneuronal uptake1 in the metabolism of 3H-noradrenaline in human dental pulp. Rabbit dental pulp was used as a reference since it was already known that normetanephrine (NMN) formation in this tissue utilised extraneuronal uptake1. Slices of pulp were preincubated in the absence and presence of 6-hydroxydopamine (1.6 mmol/l, for 10 or 20 min at pH 4.5) and subsequently incubated with 3H-noradrenaline (0.18 mumol/l for 30 min at pH 7.4). The principal metabolites formed were normetanephrine in rabbit pulp and deaminated catechols (dihydroxymandelic acid and dihydroxyphenylglycol) in human pulp. In both tissues 6-hydroxydopamine strongly inhibited formation of the deaminated catechols, but was without effect on normetanephrine formation. It is concluded that: i) in vitro 6-hydroxydopamine does not influence the metabolic process which is dependent on extraneuronal uptake1, namely normetanephrine formation in rabbit dental pulp, and ii) the deaminated catechols are largely neuronal in origin in human pulp. Attention is drawn to an unusual feature of the neuronal metabolism in human pulp, namely the appearance of dihydroxymandelic acid as the principal metabolite.

Evidence for uptake2-mediated O-methylation of noradrenaline in the human amnion FL cell-line.

The uptake and metabolism of 3H-noradrenaline has been examined in the FL cell-line derived originally from human amnion. Cell cultures metabolised 3H-noradrenaline (1.0 mumol/l) to 3H-normetanephrine and, to a lesser extent, to metabolites (not distinguished) of the O-methylated deaminated fraction; primary deaminated metabolites were not detected. 3H-normetanephrine formation a) was not saturable in the noradrenaline concentration range 0.2-150 mumol/l, b) was decreased to 20%-30% of control levels by uptake2 inhibitors (O-methylisoprenaline, 20 and 100 mumol/l; cimetidine, 10 mumol/l; hydrocortisone, 200 mumol/l) and c), was almost insensitive to uptake1 inhibitors (cocaine, 30 mumol/l; desipramine, 3 mumol/l). Uptake of noradrenaline was manifested after 30 minutes as a 6-fold increase in the cell content of the amine following inhibition of catechol-O-methyl transferase, either alone or in conjunction with inhibition of monoamine oxidase. Uptake was decreased maximally to 40% of control levels by O-methylisoprenaline. IC50 values for inhibition of the O-methylisoprenaline-sensitive component of uptake were (in mumol/l): corticosterone (0.3), papaverine (1.1), O-methylisoprenaline (3.0), cimetidine (6.0), (-)noradrenaline (460), and tetraethylammonium (2230). Except for the last agent, for which a comparative value is not available, the IC50's are in good agreement with those for inhibition of uptake2 in the Caki-1 cell-line reported by other investigators. The component of uptake resistant to O-methylisoprenaline was depressed by papaverine (a 50% decrease at 50 mumol/l), but was not affected by the other uptake2 inhibitors or by cocaine (30 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Cocaine-sensitive O-methylation of noradrenaline in dental pulp of the rabbit: comparison with the rabbit ear artery.

Incisor pulp from the rabbit metabolises exogenous noradrenaline in concentrations between 0.12 and 1.2 mumol/l mainly to NMN. Effects of chronic sympathetic denervation indicated that in incisor pulp the NMN is extraneuronal in origin, and that DOPEG and DOMA formation, as well as a major part of the noradrenaline which accumulates in the tissue, are associated with the sympathetic nerves. NMN formation was unaffected by hydrocortisone 210 mumol/l, but was strongly inhibited by cocaine 30 mumol/l. These effects contrasted with those in the rabbit ear artery, where NMN formation was increased by cocaine 30 mumol/l and decreased by hydrocortisone 210 mumol/l. In COMT-inhibited denervated pulp, cocaine inhibited the accumulation of noradrenaline. Monoamine fluorescence histochemistry of pulp exposed to noradrenaline 50 mumol/l indicated that cocaine-sensitive uptake occurred in fibroblasts. It is concluded that O-methylation of noradrenaline in dental pulp involves prior uptake of the amine by a process resembling uptake1 but which is distinguished from uptake1 by its extraneuronal location.

Distribution of extraneuronal uptake1 in reproductive tissues: studies on cells in culture.

Cultures of stromal cells from pregnant mouse uterus, and an FL cell line derived from human amnion, displayed significant capacities to O-methylate noradrenaline. O-methylation was inhibited in the stromal cells by uptake1-inhibitors, and in the FL cell line by uptake2 inhibitors. These findings are discussed in terms of the distribution and possible functional importance of catecholamine metabolising systems in the female reproductive system.