Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have determined the genetic location of the human gene encoding phenylethanolamine N-methyltransferase (PNMT), the terminal enzyme of the catecholamine pathway catalyzing the synthesis of epinephrine (adrenaline) from norepinephrine. This gene is linked to DNA markers on the long arm of chromosome 17, q21-q22, most closely to the DNA markers MFD15 (D17S250) (Zmax = 15.0, theta = 0.065) and fLB17.1 (Zmax = 14.6, theta = 0.045). Multipoint linkage analysis placed the PNMT locus in the interval fLB17.1-CMM86 (D17S74), at 4 centiMorgans (cM) distal to fLB17.1, and at 17 cM proximal to CMM86. Mapping of the PNMT gene will provide the basis for genetic linkage studies in families with disease which might pathogenetically involve this enzyme. The human chromosomal region 17q21-22 identified here to harbour the PNMT gene may be syntenic to the chromosomal region in the stroke-prone spontaneously hypertensive rat (SHR-SP) recently linked to blood-pressure regulation. As an increase of PNMT activity has been associated with the development of hypertension in SHR-SP, it will be of interest to perform comparative mapping of the PNMT gene.
Hum Mol Genet 1992 Jun
PMID:Genetic linkage of the human gene for phenylethanolamine N-methyltransferase (PNMT), the adrenaline-synthesizing enzyme, to DNA markers on chromosome 17q21-q22. 130 74

Phenylethanolamine N-methyltransferase (PNMT; EC 2.1.1.28) catalyzes the conversion of norepinephrine to epinephrine, the last step of catecholamine biosynthesis. We have previously reported molecular cloning of cDNA encoding human PNMT and chromosomal localization of its gene (Kaneda et al., J. Biol. Chem., 263 (1988) 7672-7677). In this report, we isolated the chromosomal gene encoding mouse PNMT by cross-hybridization with the human PNMT cDNA. Mouse PNMT gene spanned about 1.8 kb and consisted of 3 exons. Primer extension analysis showed two putative transcription initiation sites. Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) revealed the expression of the mouse PNMT mRNA in brain (pons and medulla oblongata) and adrenal gland. Subsequently cDNA encoding mouse PNMT was amplified by RT-PCR and cloned into the plasmid vector. Mouse PMNT gene contained the protein-coding region of 885 bp (295 amino acids) with the predicted molecular weight of 32,627. The deduced amino acid sequence of mouse PNMT revealed the major difference in the N-terminal region, as compared to the human and bovine PNMT sequences. In the 5'-terminal region of the mouse PNMT gene, we found the existence of 23 bp direct repeat sequences, which was not observed in the corresponding regions of the human and bovine PNMT genes. The presence or absence of the direct repeats caused the major difference in the PNMT sequences among species. The typical TATA, GC, and CACCC boxes as well as several sequences homologous to glucocorticoids response elements (GRE) were located in the 5'-flanking region of the mouse PNMT gene.
Brain Res Mol Brain Res 1992 May
PMID:Organization and complete nucleotide sequence of the gene encoding mouse phenylethanolamine N-methyltransferase. 132 Jul 21

Bovine phenylethanolamine N-methyltransferase (PNMT) cDNA was inserted into a bovine papilloma virus-based expression vector and used to transfect a mouse C127 cell line. The resultant recombinant bovine PNMT was characterized biochemically and immunochemically. Recombinant bovine PNMT activity, like the native bovine enzyme, was enhanced by phosphate ion in a concentration-dependent manner. Their molecular weights were shown to be identical by Western blot analysis. Antibodies raised against native bovine adrenal PNMT equally immunoprecipitated the activity of the recombinant and native enzymes. In addition, double immunodiffusion analysis showed a single precipitin line of confluence with both enzyme preparations, indicating immunological identity of native and recombinant bovine PNMT. These antibodies immunostained the recombinant enzyme protein in transfected cells and in their neurite-like processes. In addition, in situ hybridization with the bovine PNMT cDNA probe resulted in a labelling pattern similar to the immunostaining. The recombinant bovine PNMT as the native bovine enzyme exist in multiple-charge forms, but only one form is predominant. Taken together, our results suggest that recombinant bovine PNMT, expressed from bovine PNMT cDNA in a mouse cell line is enzymatically active and shares many common features with native bovine adrenal PNMT.
Brain Res Mol Brain Res 1991 Jun
PMID:Characterization of recombinant bovine phenylethanolamine N-methyltransferase expressed in a mouse C127 cell line. 165 89

The method of polymerase chain reaction was used to investigate the pre- and postmortem factors which affect the stability of specific mRNAs in the C1 region of human autopsy brain. Eight premortem and 4 postmortem factors were correlated to levels of phenylethanolamine N-methyltransferase (PNMT), three splice forms of amyloid precursor protein (APP) and actin mRNAs in 10 control brains using Pearson's correlation coefficient. Significant negative correlations were found between hypoxia and PNMT mRNA, and between postmortem and storage intervals and APP751 and beta-actin mRNAs. A positive correlation was found between death-refrigeration interval and total APP and APP695 mRNAs. There was also a positive correlation between seizure activity and APP770 mRNA. The results indicate that a variety of pre- and postmortem factors can affect mRNA levels. The possible effect of pre- and postmortem factors on specific mRNA levels should be investigated prior to comparing mRNA levels in different disease states.
Brain Res Mol Brain Res 1991 Aug
PMID:Effect of pre- and postmortem variables on specific mRNA levels in human brain. 166 43

Primary cultures of chromaffin cells were prepared from bovine adrenal medullae and the levels of mRNA for tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT) determined. The cells expressed moderate levels of TH mRNA and low levels of PNMT mRNA. The latter appeared to be more sensitive than TH mRNA to variations in the culture medium. The treatment of cultures with agents that activate signal transduction pathways, forskolin or phorbol esters, dramatically enhanced the expression of both mRNAs. The forskolin-induced increases in the steady-state levels of TH and PNMT mRNAs occurred rapidly and were apparent within 5 hours. These data suggest that the TH and PNMT genes can be regulated by second messengers. In contrast, dexamethasone treatment dramatically increased PNMT mRNA with no change in TH mRNA. The increase in PNMT mRNA was apparent within 6 hours of addition of the drug to the culture medium.
J Mol Neurosci 1991
PMID:Differential and coordinate regulation of TH and PNMT mRNAs in chromaffin cell cultures by second messenger system activation and steroid treatment. 172 44

The expression of proenkephalin A (ProEnk A) mRNA and phenylethanolamine N-methyltransferase (PNMT) mRNA in response to nicotine and to a number of secretagogues was examined in cultured bovine adrenal chromaffin cells. Prolonged incubation with nicotine (10 microM) resulted in a 2-fold increase in ProEnk A mRNA but had no significant effect on the level of PNMT mRNA. Similarly, prolonged stimulation with high K+ (56 mM) induced a time-dependent elevation in the level of ProEnk A mRNA reaching 4-fold basal level after 24 h incubation. By contrast, the level of PNMT mRNA was not changed by treatment with high K+. The increase in the level of ProEnk A mRNA by high K+ was abolished by the presence of 10 microM D600, a calcium channel blocker. Unlike the effects of high K+, treatment of the cells with the sodium channel activator veratridine significantly elevated the levels of both ProEnk A and PNMT mRNA. This increase in ProEnk A and PNMT mRNA levels was however less affected by D600. Stimulation of the cells with Ba2+ (1.1 mM) also stimulated the levels of ProEnk A and PNMT mRNA and this action required the presence of extracellular Ca2+. This was in contrast to the effect of Ba2+ in stimulating catecholamine secretion, which was inhibited by Ca2+ and enhanced in Ca2(+)-free buffer. The results of the present study indicate that membrane depolarization and entry of extracellular Ca2+ play an important role on the regulation of ProEnk A and PNMT mRNAs, in addition to their well-known actions on hormone secretion. Furthermore, these results suggest that the expression of ProEnk A mRNA and PNMT mRNA are under independent regulation in response to secretory stimulation.
Brain Res Mol Brain Res 1991 Jan
PMID:Coordinate and differential regulation of proenkephalin A and PNMT mRNA expression in cultured bovine adrenal chromaffin cells: responses to secretory stimuli. 185 66

The expression of proenkephalin A (ProEnk A) mRNA and phenylethanolamine N-methyltransferase (PNMT) mRNA in response to cAMP analogues, forskolin and phorbol esters was examined in cultures of bovine adrenal chromaffin cells. Exposure of chromaffin cells to 1 mM dibutyryl cAMP for 24 h increased significantly the levels of ProEnk A mRNA, with no significant effect on the levels of PNMT mRNA. Cells exposed to the tumor promoting phorbol esters (phorbol 12-myristate 13-acetate, phorbol 12,13-dibutyrate or 4-beta-phorbol 12,13-didecanoate) for 12 h differentially activated PNMT mRNA and ProEnk A mRNA expression. The levels of PNMT mRNA were dramatically elevated in response to low concentrations (10(-9) to 10(-8)M) of these phorbol esters, but these increases were diminished at higher concentrations (10(-7) to 10(-6) M) of the phorbol esters. These responses were synergistically potentiated by dexamethasone (1 microM), a synthetic glucocorticoid. None of these effects was seen with the biologically inactive phorbol ester, 4-alpha-phorbol 12,13-didecanoate. By contrast, the expression of ProEnk A mRNA was activated by the tumor promoting phorbol esters in a concentration-dependent manner. The results of this study demonstrate a differential stimulatory effect of second messenger mechanisms in the control of PNMT and ProEnK A mRNA expression and provide further evidence for an independent control for the enkephalin and adrenaline synthesis in these cells.
Brain Res Mol Brain Res 1991 Jan
PMID:Coordinate and differential regulation of proenkephalin A and PNMT mRNA expression in cultured bovine adrenal chromaffin cells: responses to cAMP elevation and phorbol esters. 185 68

Cold stress is known to increase the synthesis and release of catecholamines in the sympathoadrenal system. Previously, we have demonstrated that cold exposure results in a 3- to 4-fold increase in adrenomedullary tyrosine hydroxylase (TH) activity, which is mediated by concomitant alterations in TH mRNA and protein levels. To further investigate the effects of stress on the expression of the catecholamine biosynthetic enzymes, we have isolated a rat cDNA clone encoding the epinephrine-synthesizing enzyme phenylethanolamine N-methyltransferase (PNMT). The cDNA clone is 905 nucleotides in length and contains a single open reading frame corresponding to 270 amino acids. The amino acid sequence predicted from this nearly full-length cDNA is 89% and 86% identical to that of bovine and human PNMT, respectively. Using the rat PNMT cDNA as a hybridization probe, we have measured the effects of cold stress on the relative abundance of adrenomedullary PNMT mRNA. Levels of PNMT protein were also estimated using an immunoblot analysis. As in the case of TH, cold exposure resulted in a rapid and prolonged increase in PNMT mRNA abundance, followed by concomitant increases in PNMT immunoreactivity. However, there appear to be quantitative and qualitative differences in the adaptive response of TH and PNMT to cold stress.
Brain Res Mol Brain Res 1989 Nov
PMID:Isolation of a rat adrenal cDNA clone encoding phenylethanolamine N-methyltransferase and cold-induced alterations in adrenal PNMT mRNA and protein. 257 95

The conformational and steric aspects of binding to phenylethanolamine N-methyltransferase (PNMT; EC 2.1.1.28) for phenylethanolamine substrates and phenylethylamine inhibitors were probed with three conformationally defined analogues (11, 12, and 13) of phenylethylamine (1) and phenylethanolamine (6) containing the benzobicyclo[3.2.1]octane skeleton. The 2-aminotetralin (2AT) moiety in conformationally defined analogues 11, 12, and 13 exists in a half-chair conformation with an equatorial amino group. Although conformationally restricted phenylethylamine analogue 2AT (3, Ki = 6.8 microM) and conformationally restricted phenylethanolamine analogues (cis)- and (trans)-2-amino-1-tetralol (9, Km = 22 microM; Vmax = 0.15; 100 X Vmax/Km = 0.68; 10, Ki = 9.4 microM) are good ligands for PNMT, none of the analogues 11, 12, and 13 showed activity as a substrate of PNMT. The fact that 11 (Ki = 206 microM) is more potent than analogues 4 (Ki = 1296 microM) and 5 (Ki = 479 microM), with a half-boat 2AT moiety, suggests that PNMT preferentially binds the half-chair conformation of 2AT at the active site. This is consistent with previous findings that a fully extended conformation for the aminoethyl side chain of phenylethylamine inhibitors is optimal for PNMT binding. The reduced activity of 11, 12 (Ki = 1246 microM), and 13 (Ki = 3000 microM), compared with 2AT and (cis)- and (trans)-2-amino-1-tetralol (9 and 10) is consistent with a negative steric interference from the extra ethano bridge in 11, 12, and 13. The results from 11, 12, and 13, combined with previous findings, suggest that PNMT interacts better with relatively planar ligands.
Mol Pharmacol 1989 Jan
PMID:Conformational and steric aspects of phenylethanolamine and phenylethylamine analogues as substrates or inhibitors of phenylethanolamine N-methyltransferase. 291 86

Chromogranin A is a highly acidic protein that is found in the secretory granules of many endocrine and neuronal cells. To localize bovine cell populations involved in chromogranin A biosynthesis, the distribution of the mRNA encoding this protein was determined with in situ hybridization histochemistry. In the adrenal gland, the mRNA was found in the chromaffin cells of the medulla but was absent from the cortex. The distribution of the mRNA in the medulla was uneven; cells located at the periphery were more heavily labeled than those in the center of the gland. Because the adrenal medulla is composed of several cell types, the chromogranin A-containing cells were further characterized for the presence of neuropeptide and adrenergic markers. Adjacent sections were examined for the mRNAs encoding enkephalin and phenylethanolamine N-methyltransferase (PNMT), the enzyme that catalyzes the formation of epinephrine from norepinephrine. Both mRNAs were present in a narrow band of cells at the periphery of the medulla. However, in contrast to the distribution of chromogranin A mRNA, the enkephalin and PNMT mRNAs were detected in only a small number of cells in the inner medullary region. The difference in the distribution of the enkephalin and PNMT mRNAs from that of chromogranin A suggests that the expression of these genes is differentially regulated. In addition to the adrenal gland, chromogranin A mRNA is expressed by many other tissues. In the parathyroid gland, which is rich in the mRNA but exhibits little chromogranin A-like immunoreactivity, the message was present in most cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Endocrinol 1988 Apr
PMID:Chromogranin A biosynthetic cell populations in bovine endocrine and neuronal tissues: detection by in situ hybridization histochemistry. 338 Jan 4


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