Regulation of histidine decarboxylase activity in rat hypothalamusin vitro by ATP and cyclic AMP: Enzyme inactivation under phosphorylating conditions

Huszti, Z.; Magyar, K.

doi:10.1007/bf01973868

Cited by 11 publications

(5 citation statements)

References 11 publications

(13 reference statements)

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“…Third, sequence analysis of HDC also revealed two potential sites of phosphorylation that closely fit the consensus recognition sequence of cAMP-dependent protein kinase (28). This finding supports the in vitro studies, suggesting that phosphorylation of brain HDC by cAMP-dependent protein kinase leads to enzyme inactivation (43). Also, each of the two HDC mRNA species (major 2.7 kb and minor 3.5 kb) as revealed by Northern hybridization analysis (unpublished results) could encode unique proteins (i.e., alternative splicing of RNA transcripts).…”

Section: Discussionsupporting

confidence: 78%

Characterization and expression of the complementary DNA encoding rat histidine decarboxylase.

Joseph

Sullivan

Wang

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

159

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Histamine is a neurotransmitter in the central The biogenic amine histamine is a neurotransmitter in the central nervous system and an important physiological modulator of gastric acid secretion, airway smooth-muscle tone, vasomotor control, inflammation, and allergic reactions (1-3). The formation of histamine from its precursor histidine is catalyzed by the enzyme L-histidine decarboxylase (HDC; L-histidine carboxy-lyase, EC 4.1.1.22). In rodents the enzyme is primarily localized in the brain (hypothalamic neurons and projections to other brain regions) (4), the glandular regions of the stomach (5), mast cells (6), and fetal liver (7). HDC has been purified from rat stomach (5) and fetal liver (7) and was shown to be a dimer consisting ofMr 54,000 subunits. Like other mammalian amino acid decarboxylases, the enzyme utilizes pyridoxal phosphate as a coenzyme. Although no primary amino acid sequence of mammalian or other eukaryotic HDC is known, immunological studies indicated that rodent HDC is closely related to L-dopa decarboxylase (DDC) (8). In this manuscript we present the amino acid sequence of rat HDC as deduced from the fetal liver cDNA11and demonstrate its close homology to DDC, but not to other characterized amino acid decarboxylases. EXPERIMENTAL PROCEDURESPreparation and Screening of cDNA Library. Poly(A)+ RNA from fetal liver (16 days after conception) was prepared by guanidine thiocyanate extraction (9) and transcribed with avian myeloblastosis virus reverse transcriptase. The second strand was synthesized with RNase H and Escherichia coli DNA polymerase I (10). After treatment with T4 DNA polymerase to flush the ends, EcoRI linkers were applied by ligation and cleaved with EcoRI. Gel filtration (Sepharose CL-4B)-purified cDNA was ligated with dephosphorylated EcoRI-cleaved phage A gt11 DNA, and the recombinants were packaged in vitro (11). The unampliflied library was screened on E. coli Y1088, with [32P]DNA as previously described (12). Positive recombinants were plaque-purified, and the DNA inserts were isolated by electroelution.Transient Expression in Monkey Kidney Cells. The DNA inserts from isolates HDC-18 and HDC-21 were cloned into the expression vector pCMV5, a modified pCMV plasmid (13) containing an EcoRI cloning site (the modified plasmid was from David Russel and Matthew Lorence, University of Texas Southwestern Medical Center, Dallas). This plasmid vector contains the cytomegalovirus (CMV) promoterenhancer of the immediate early gene, the poly(A)+ additiontranscription terminator region of the human growth hormone gene, the simian virus 40 origin of replication, and a polylinker region for the insertion of cDNAs (13). Recombinants with the correct orientation for expression were identified by restriction endonuclease analysis, and the plasmid DNA (pCMVHDC-18 and pCMVHDC-21) was purified by CsCl/ethidium bromide centrifugation. For transfection, subconfluent COS 7 cells (106 cells per 100-mm dish) were transfected with 5 ug of pCMV DNA per dish by the DEAE-dextran method (14)...

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Section: Discussionsupporting

confidence: 78%

Characterization and expression of the complementary DNA encoding rat histidine decarboxylase.

Joseph

Sullivan

Wang

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

159

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“…Recently, we demonstrated that hypothalamic HD in a homogenate could strikingly be inhibited by cAMP, under the circumstances, favourable for a cAMP-dependent phosphorylation [1 ]. Present data strengthens the participation of cAMP-dependent PK in this action and additionally shows the direct or indirect involvement of the cyclic GMP system in the 'up-regulation' of histamine formation.…”

Section: Introductionsupporting

confidence: 78%

“…In preliminary experiments, inhibition of HD activity by cAMP, was established in a homogenate of the hypothalamus under phosphorylating conditions [1]. For further studies, a 20,000 g supernatant fraction of a sustained homogenate, 200 mg tissue per ml phosphate buffer (pH 6.5), Table 1 The effect of endogeneous and exogeneous cAMP on HD activity in a 20,000 g supernatant of a sustained homogenate of the hypothalamus.…”

Section: Resultsmentioning

confidence: 99%

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Evidence for the role of cAMP-dependent protein kinase in the down-regulation of hypothalamic HD: Reversal of cAMP-(ATP) induced inhibition of HD activity by the ‘Walsh’ inhibitor of cAMP-dependent protein kinase and by cyclic GMP

Huszti

Magyar

1985

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Under the total blockade of PDE1 and the presence of endogeneous ATP and MgCl2, the inhibitory effect of cAMP on HD activity could be demonstrated as low as 8.7 X 10(-8) M concentration in a 20,000 g supernatant of a sustained homogenate of rat hypothalamus. A total reverse of this action and also a partial release of the cAMP-induced inhibition of HD, occurred at higher concentrations of cAMP, and ATP could be achieved by an endogeneous inhibitor of cAMP-dependent protein kinase or by cyclic GMP. The reversal of cAMP action by PKI seems to serve a strong evidence for the role of cAMP-dependent protein kinase (EC 2.7.37: ATP-protein phosphotransferase) in this action and emphasized the involvement of a direct or an indirect phosphorylation in the regulation of HD activity. The stimulatory effect of cyclic GMP on cAMP-induced inhibition of HD or its 'direct' effect on histamine formation is asserted, probably through the activation of PDE, or through independent stimulatory machinery, coupled to the cyclic GMP system.

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“…KOLLONITSCH et al developed ~-fluoromethylhistidine [20] as an irreversible inhibitor of HDC and its mechanism was studied [13]. Recently, HUSZTI and MAGYAR reported that HDC was phosphorylated by cyclic AMPdependent protein kinase resulting in decrease of the activity [21]. An antizyme that is a specific inhibitor of ornithine decarboxylase (EC 4.1.1.17) [15] had no effect on HDC activity under conditions inhibiting ornithine decarboxylase (Y. Taguchi et al, unpublished).…”

Section: Discussionmentioning

confidence: 95%

Effects of various compounds on histidine decarboxylase activity: Active site mapping

et al. 1985

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The effect of about one hundred compounds on the activity of histidine decarboxylase partially purified from whole bodies of fetal rats was determined. Most of them at their 10 mM concentration had little effect on the enzyme activity; but 12 compounds inhibited the enzyme to a greater extent than 30%. Among these, except for alpha-methylhistidine that has been known to be a strong and specific inhibitor, DOPA, homocysteine, cysteine, methionine and urocanic acid were the best inhibitors; beta-phenyllactic acid, phenylpyruvic acid and carnosine were less strong inhibitors; valine, oxaloacetic acid and N tau-methylimidazole acetic acid were weak inhibitors. Histamine had no inhibitory action. Thus, the substrate binding site of histidine decarboxylase is very rigid and specific for L-histidine.

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Regulation of histidine decarboxylase activity in rat hypothalamusin vitro by ATP and cyclic AMP: Enzyme inactivation under phosphorylating conditions

Cited by 11 publications

References 11 publications

Characterization and expression of the complementary DNA encoding rat histidine decarboxylase.

Characterization and expression of the complementary DNA encoding rat histidine decarboxylase.

Evidence for the role of cAMP-dependent protein kinase in the down-regulation of hypothalamic HD: Reversal of cAMP-(ATP) induced inhibition of HD activity by the ‘Walsh’ inhibitor of cAMP-dependent protein kinase and by cyclic GMP

Effects of various compounds on histidine decarboxylase activity: Active site mapping

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