Disease relevance of Pnmt

• We did not identify any sequence differences between the Wistar-Kyoto rats and SHRSP in the primary structure, in 1077 bp of the 5'-flanking region, or in the 256-bp 3'-end region, making Pnmt an unlikely gene for the genetic basis of salt-loaded hypertension [1].
• Association between the phenylethanolamine N-methyltransferase gene and multiple sclerosis [2].
• Recurrent hypoglycemia further impairs epinephrine counterregulation and is also associated with reduced phenylethanolamine N-methyltransferase mRNA [3].
• Effects of chronic prenatal hypoxia on tyrosine hydroxylase and phenylethanolamine N-methyltransferase messenger RNA and protein levels in medulla oblongata of postnatal rat [4].
• The expression of PNMT has generally been thought to occur in amacrine cells of the ganglion cell and inner nuclear layers [5].

High impact information on Pnmt

• Medullas explanted to culture exhibited a 50-fold rise in [Leu]enkephalin in 4 days, whereas tyrosine hydroxylase remained constant, and phenylethanolamine-N-methyltransferase decreased to a new baseline level [6].
• Conversely, alpha-adrenergic receptor density in brain regions containing phenylethanolamine N-methyltransferase is two to three times lower in F344 rats than in BUF rats; alpha-receptors in frontal cortex (a brain region lacking phenylethanolamine N-methyltransferase activity and epinephrine) are similar in both strains [7].
• It was found that the activity of adrenomedullary and regional brain phenylethanolamine N-methyltransferase is at least four times higher in F344 rats than in BUF rats; these strain-dependent differences corresponded directly with the epinephrine content of the medulla-pons and hypothalamus [7].
• We studied the time-course and mechanism by which the glucocorticoid dexamethasone increases muscle PNMT activity [8].
• Rat skeletal muscle contains two enzymes which can make epinephrine: phenylethanolamine N-methyltransferase (PNMT) and nonspecific N-methyltransferase [8].

Chemical compound and disease context of Pnmt

• In studies of adrenal tissue from separate rats, antecedent hypoglycemia decreased adrenal EPI content but did not significantly alter the expression of TH, phosphorylated TH, or phenylethanolamine N-methyltransferase [9].
• When rats were pretreated with 2,3-dichloro-alpha-methylbenzylamine, an inhibitor of phenylethanolamine N-methyltransferase, the enzyme catalyzing the formation of epinephrine from norepinephrine, 80 mg/kg i.p. before decapitation, the l-propranolol-induced decrease was abolished completely.(ABSTRACT TRUNCATED AT 250 WORDS)[10]
• The mechanisms sustaining high blood pressure in conscious one-kidney, one-clip Goldblatt rats were evaluated with the use of SK&F 64139, a phenylethanolamine N-methyltransferase inhibitor capable of crossing the blood-brain barrier and of captopril, an angiotensin converting enzyme inhibitor [11].
• To characterize the effects of prenatal hypoxia on subsequent TH and PNMT gene and protein expression, pregnant rats were placed in moderate hypoxia (10% O2) from gestational d 18 until birth [4].
• PNMT-containing neurons in the rostral medulla oblongata (C1, C3 groups) are transneuronally labelled after injection of herpes simplex virus type 1 into the adrenal gland [12].

Biological context of Pnmt

• Homodimerization of the glucocorticoid receptor is not essential for response element binding: activation of the phenylethanolamine N-methyltransferase gene by dimerization-defective mutants [13].
• In transfection assays, PNMT promoter activation by Sp1 and MAZ depends on promoter length, with -893 bp of sequence yielding greatest activation [14].
• Thus, expression of the PNMT gene seems to be modulated through competitive binding of phosphorylated Sp1 and MAZ to their consensus elements in the promoter [14].
• In humans, the gene encoding phenylethanolamine N-methyltransferase (PNMT) was localized near the angiotensin-converting enzyme gene on human chromosome 17 [1].
• The rat phenylethanolamine N-methyltransferase (PNMT) gene promoter contains 1-base pair (bp) overlapping consensus sequences for Sp1 and MAZ transcription factors at -48 and -38 bp, respectively [14].

Anatomical context of Pnmt

• With the use of a somatic cell hybrid panel and genetic mapping techniques, Pnmt mapped within the confidence interval that contains Bp1 [1].
• Utilizing the peroxidase Fab/[125I]protein A method, we present here the first direct evidence that PNMT is present in many endings also containing NPY in the thalamic and hypothalamic paraventricular nuclei and in the arcuate nucleus [15].
• Morphometrical and microdensitometrical studies on phenylethanolamine-N-methyltransferase- and neuropeptide Y-immunoreactive neurons in the rostral medulla oblongata of the adult and old male rat [16].
• Analysis revealed that the acetylcholinesterase-immunoreactive chromaffin cell groups lacked phenylethanolamine-N-methyltransferase staining both in controls and treated rats [17].
• The phenylethanolamine-N-methyltransferase- and neuropeptide Y-immunoreactive nerve terminal profiles and the glucocorticoid receptor-immunoreactive nuclear profiles have been characterized in the parvocellular part of the paraventricular hypothalamic nucleus of the adult (3 month) and the old (24 month) male rat [18].

Associations of Pnmt with chemical compounds

• A 15% haemorrhage significantly induced expression of PNMT in the rostral C1 region and NPY in the caudal C1 and A1 regions but had no effect on ENK at any sites, suggesting a differential regulation on the expression of these three genes in the VLM [19].
• After two months, grafts were examined for the presence of immunoreactivity (IR) and catalytic activity to the epinephrine-synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT, E.C. 2.1.1.28), a specific adrenergic marker [20].
• Nicotine treatment upregulated the expression of TH, PNMT, and NPY genes in a dose-dependent fashion [21].
• Phenylethanolamine N-methyltransferase (PNMT) is the enzyme that synthesizes epinephrine from norepinephrine [22].
• NPY-LI in the adrenaline cells of the cat was clearly separated from the neurotensin-LI in the noradrenaline dopamine-beta-hydroxylase-positive, PNMT-negative cells [23].

Regulatory relationships of Pnmt

• Although PACAP stimulates rapid changes in transcription factor expression and PNMT promoter activity, its effects are long lasting [24].
• Role of transcription factor Egr-1 in phorbol ester-induced phenylethanolamine N-methyltransferase gene expression [25].

Other interactions of Pnmt

• NPY immunoreactive nerve terminal profiles were much more affected than the PNMT immunoreactive profiles during aging as revealed by a marked reduction in the number of profiles and by a marked reduction of absorbency values in the microdensitometrical analysis [26].
• Dual-colour indirect-labelled immunofluorescence was used to localise phenylethanolamine N-methyltransferase (PNMT) and the adrenomedullin receptor in the same section [27].
• Immunocytochemical localization of tyrosine hydroxylase, dopamine-beta-hydroxylase and phenylethanolamine-N-methyltransferase in the adrenal glands of the frog and rat by a peroxidase-antiperoxidase method [28].
• Differential activation of the rat phenylethanolamine N-methyltransferase gene by Sp1 and Egr-1 [29].
• Immunocytochemical identification showed that the grafts contained chromaffin cells with a choline acetyltransferase stainings while, in parallel, phenylethanolamine-N-methyltransferase stainings seemed to be decreased [30].

Analytical, diagnostic and therapeutic context of Pnmt

• Single immobilization for 2 h increased gene expression of PNMT in both atria and ventricles [22].
• Adrenalectomy or hypophysectomy completely prevented the immobilization-induced increase in spleen PNMT mRNA levels, suggesting that stress-induced PNMT gene expression in the spleen is regulated predominantly via pituitary-adrenocortical axis [31].
• Both Southern blot and sequencing verified the specificity of PNMT detected by RT-PCR [22].
• In atria, this effect was clearly modulated by glucocorticoids, because either adrenalectomy or hypophysectomy prevented the increase in PNMT mRNA levels in response to immobilization stimulus [22].
• Gene expression of phenylethanolamine N-methyltransferase (PNMT), the enzyme catalyzing conversion of norepinephrine to epinephrine, has been detected in rat spleen using the reverse transcription polymerase chain reaction [31].

References