Disease relevance of PNMT

• Conversely, the PNMT mRNA concentration in the pheochromocytomas was lower than that in the normal adrenal medullas [1].
• Dopamine beta hydroxylase (DBH), The noradrenaline-synthesizing enzyme, and phenyl-ethanolamine-N-methyltransferase (PNMT), the adrenaline-synthesizing enzyme, were assayed in 18 areas of brain stem in eight cases of parkinsonian syndromes and of four age- and postmortem delay-matched controls [2].
• Immunohistochemical study of catecholamine synthesizing enzymes tyrosine hydroxylase (TH) and phenylethanolamine-N-methyl transferase (PNMT) was performed in lower brain stem of 5 controls and 9 sudden infant death "syndrome" (SIDS) cases [3].
• Phenylethanolamine N-methyltransferase-like immunoreactivity in psoriasis. An immunohistochemical study on catecholamine synthesizing enzymes and neuropeptides of the skin [4].
• Transcriptional regulation of phenylethanolamine N-methyltransferase in pheochromocytomas from patients with von hippel-lindau syndrome and multiple endocrine neoplasia type 2 [5].

Psychiatry related information on PNMT

• Given the importance of the swine (Sus scrofa) as an animal model for human development, physiology and disease, neurons containing the epinephrine-synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT), were mapped in the medulla oblongata of neonatal swine as a first step in identifying their roles in central autonomic control [6].
• Phenylethanolamine N-methyltransferase activity is decreased in Alzheimer's disease brains [7].

High impact information on PNMT

• The administration of a phenylethanolamine N-methyltransferase inhibitor to experimentally hypertensive animals caused a reduction of the elevated blood pressure to normal values [8].
• The adrenaline-forming enzyme (phenylethanolamine N-methyltransferase) was elevated in the A1 and A2 regions of the brainstem of 4-week-old spontaneously (genetic) hypertensive rats and in the A1 region of adult experimentally (deoxycorticosterone acetate and sodium chloride) hypertensive rats [8].
• The mice carry the SV40 T-antigen under the control of 5' flanking sequences from the human phenylethanolamine N-methyltransferase (PNMT) gene in order to target oncogene expression to adrenergic cell types [9].
• The phenylethanolamine N-methyltransferase immunopositivity disappears by day 35, while a small amount of tyrosine hydroxylase-positive cells still can be found in the adult [10].
• RNA blot-hybridization analysis showed the presence of phenylethanolamine N-methyltransferase mRNA in the amygdala and the bed nucleus of the stria terminalis in the young and in the adult rat brain [10].

Chemical compound and disease context of PNMT

• Pheochromocytomas in multiple endocrine neoplasia type 2 (MEN-2) express phenylethanolamine N-methyltransferase (PNMT), the enzyme that catalyzes conversion of norepinephrine to epinephrine, whereas those in von Hippel-Lindau (VHL) syndrome do not [5].
• CONCLUSIONS: These findings indicate that adrenaline production in adrenaline-secreting pheochromocytomas is primarily controlled by the level of PNMT gene expression, and that the gene expression may be enhanced by both cortisol and Egr-1 [11].

Biological context of PNMT

• These findings suggest that neonatal melatonin administration induces an earlier sexual maturation in male rats, possibly related to PRL, LH, MAO, and PNMT increases [12].
• This study examined whether transcription factors known to regulate expression of PNMT explain the different tumor phenotypes in these syndromes [5].
• Microarray analysis, however, did indicate differences in expression of genes involved in neural crest cell lineage and chromaffin cell development, consistent with differential survival of PNMT-expressing cells in the two syndromes [5].
• Using the reverse transcription polymerase chain reaction, we detected a single form of phenylethanolamine N-methyltransferase (PNMT) mRNA in hypothalamus and medulla/pons and two forms in cerebellum [13].
• Mechanism responsible for the regulation of stress-induced increase of PNMT gene expression in cardiac atria is clearly dependent on the presence of glucocorticoids [14].

Anatomical context of PNMT

• Thus, we hypothesized that replacement of the sulfonamide -NH- with a methylene group could result in compounds that would retain potency at PNMT and that would have increased lipophilicity, thus increasing the likelihood they will cross the blood brain barrier [15].
• Chromaffin cells from all three species reacted for TH, DBH and PNMT in co-culture and were histo-fluorescent [16].
• The neuroblasts of the ganglia showed intense peroxidase immunoreactivity for TH, moderate reaction to DBH, and no reaction to PNMT [17].
• With anti-PNMT antibody, electively in nucleus gelatinosus (NG), a subnucleus of nucleus tractus solitarius, an absence of immunoreactivity was noticed [3].
• Epinephrine synthesis was similar in keratinocytes from uninvolved epidermis and controls, but cells from involved skin had 6.5-fold less epinephrine than controls, indicative of low phenylehtanolamine-N-methyl transferase (PNMT) activity [18].

Associations of PNMT with chemical compounds

• Sulfone 24 (hPNMT Ki = 1.3 microM) is the most potent compound in this series and is quite selective for PNMT versus the alpha2-adrenoceptor, but 24 is less potent than the corresponding sulfonamide, 16 (hPNMT Ki = 0.13 microM) [15].
• Early neonatal melatonin administration increased MAO B and PNMT activities on day 45 [12].
• Control animals showed very few (5.5%) PNMT/Fos co-localized neurons in the C1 adrenergic cell group [19].
• PNMT with norepinephrine as substrate was also significantly decreased in parkinsonian brains [20].
• Low, but detectable, phenylethanolamine N-methyltransferase (PNMT) activity was observed in PC12 cells, and dexamethasone increased its activity 5.6-fold at 72 h [21].

Regulatory relationships of PNMT

• The mechanism by which nerve growth factor (NGF) regulates adrenergic expression was examined in PC-12 cells transfected with a rat phenylethanolamine N-methyl-transferase (PNMT) promoter-luciferase reporter gene construct pGL3RP893 [22].

Other interactions of PNMT

• We evaluated the activity of phenylethanolamine-N-methyltransferase (PNMT) and dopamine-beta-hydroxylase (DBH) in 16 pheochromocytomas [23].
• Cell extracts from epidermal suction blister roofs revealed only half the normal activity of phenylethanolamine-N-methyl transferase (PNMT) together with a threefold induction of the norepinephrine-degrading enzyme monoamine oxidase A (MAO-A) [24].
• Plasma and urinary epinephrine and norepinephrine are detected by conversion to metanephrine with the enzymes catechol-O-methyl-transferase (COMT) and phenylethanolamine-N-methyltransferase (PNMT) [25].
• NGF treatment increased PNMT promoter-driven luciferase activity in a dose- and time-dependent manner [22].
• The catecholamine-forming and metabolizing enzyme tyrosine hydroxylase, dopa decarboxylase, dopamine-beta-hydroxylase, phenylethanolamine N-methyltransferase, and catecholamine-O-methyltransferase, as well as the endogenous inhibitor of dopamine-beta-hydroxylase were compared in the brains of schizophrenics and controls [26].

Analytical, diagnostic and therapeutic context of PNMT

• PNMT mRNA was localized with in situ hybridization throughout the thymus, but levels were approximately twofold higher in the cortex than in the medulla [27].
• Both Southern blot and sequencing verified the specificity of PNMT detected by RT-PCR [14].
• The main aim of this study was to determine the localization of the PNMT mRNA in the heart and to examine whether gene expression of this enzyme is affected by immobilization (IMO) stress in a time-dependent manner [14].
• Molecular cloning of cDNA and chromosomal assignment of the gene for human phenylethanolamine N-methyltransferase, the enzyme for epinephrine biosynthesis [28].
• The distribution of PNMT activity in the rat brain correlates with the distribution of PNMT immunofluorescence [29].

References