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Biomedical subjects

Susumu Ueno

Publications and source records attributed to Susumu Ueno.

At least 19 recordsLinked to original sources
PubMed2006

Capsaicin inhibits catecholamine secretion and synthesis by blocking Na+ and Ca2+ influx through a vanilloid receptor-independent pathway in bovine adrenal medullary cells.

We report here the effects of capsaicin, a flavoring ingredient in the hot pepper Capsicum family, on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. Capsaicin inhibited catecholamine secretion (IC(50)=9.5, 11.8, and 62 microM) stimulated by carbachol, an agonist of the nicotinic acetylcholine receptor, by veratridine, an activator of voltage-dependent Na(+) channels, and by high K(+), an activator of voltage-dependent Ca(2+) channels, respectively. Capsaicin also suppressed carbachol-induced (22)Na(+) influx (IC(50)=5.0 microM) and (45)Ca(2+) influx (IC(50)=24.4 muM), veratridine-induced (22)Na(+) influx (IC(50)=2.4 microM) and (45)Ca(2+) influx (IC(50)=1.1 microM), and high K(+)-induced (45)Ca(2+) influx (IC(50)=5.8 microM). The reduction in catecholamine secretion caused by capsaicin was not overcome by increasing the concentration of carbachol. Furthermore, capsazepine (10 microM), a competitive antagonist for the transient receptor potential vanilloid 1, and ruthenium red (30 microM), a nonselective cation channel antagonist, did not block the inhibition by capsaicin of catecholamine secretion. Capsaicin also suppressed both basal and carbachol-stimulated (14)C-catecholamine synthesis (IC(50)=10.6 and 26.4 microM, respectively) from [(14)C] tyrosine but not from L: -3, 4-dihydroxyphenyl [3-(14)C] alanine ([(14)C] DOPA) as well as tyrosine hydroxylase activity (IC(50)=8.4 and 39.0 microM, respectively). The present findings suggest that capsaicin inhibits catecholamine secretion and synthesis via suppression of Na(+) and Ca(2+) influx through a vanilloid receptor-independent pathway.

Adrenal Medulla↗
PubMed2006

New approach to risk assessment of central neurotoxicity induced by 1-bromopropane using animal models.

1-Bromopropane (1-BP) induces central as well as peripheral neurotoxicity in workers. We have reported the dysfunction of feedback inhibition (i.e. disinhibition) in the rat hippocampus following exposure to 1-BP at concentrations of 1500 and 700 ppm. For risk assessment, we studied disinhibition of the CA1 region and the dentate gyrus in hippocampal slices obtained from control and 1-BP-exposed (200 and 400 ppm) rats, and determined the bromide concentration in the brain. Granule cell disinhibition was observed after inhalation exposure to 400 ppm 1-BP for 8 or 12 weeks, suggesting that the dentate gyrus was more sensitive than the CA1 region to 1-BP exposure. The lowest observed adverse effect level and the no observed adverse effect level of 1-BP inhalation for disinhibition were 400 and 200 ppm, respectively. The concentration of bromides in the brain increased from 2.9+/-1.5 to 85.0+/-25.4 microg/g-wet brain at week 4 of 400 ppm inhalation, and no further increase was observed even when the exposure period was extended for up to 12 weeks. The relationship between total dose (ppm-h) and the exposure concentration of 1-BP was investigated at different exposure concentrations. Disinhibition and death by inhalation depended on the total dose, and their occurrence appeared earlier as the exposure concentration increased. The results demonstrated a novel model for risk assessment of central neurotoxicity induced by 1-BP inhalation.

Air Pollutants↗
PubMed2006

Changes in the function of the inhibitory neurotransmitter system in the rat brain following subchronic inhalation exposure to 1-bromopropane.

1-Bromopropane (1-BP) has been widely used as a cleaning agent and a solvent in industries, but the central neurotoxicity of 1-BP remains to be clarified. In the present study, we investigated the effects of subchronic inhalation exposure to 1-BP vapor on the function of the inhibitory neurotransmitter system mediated by gamma-aminobutyric acid (GABA) in the rat brain. Male Wistar rats were exposed to 1-BP vapor for 12 weeks (6h/day, 5 days/week) at a concentration of 400 ppm, and, in order to investigate the expression and function of brain GABA type A (GABAA) receptors, total/messenger RNA was prepared from the neocortex, hippocampus, and cerebellum of the control and 1-BP-exposed rats. Moreover, hippocampal slices were prepared, and the population spike (PS) amplitude and the slope of the field excitatory postsynaptic potential (fEPSP) were investigated in the paired-pulse configuration of the extracellular recording technique. Using the Xenopus oocyte expression system, we compared GABA concentration-response curves obtained from oocytes injected with brain subregional mRNAs of control and 1-BP exposed rats, and observed no significant differences in apparent GABA affinity. On the other hand, paired-pulse inhibition of PS amplitude was significantly decreased in the hippocampal dentate gyrus (DG) by exposure to 1-BP, without any effect on the paired-pulse ratio of the fEPSP slopes, suggesting neuronal disinhibition in the DG. Moreover, RT-PCR analysis indicated decreased levels of GABAA receptor beta3 and delta subunit mRNAs in the hippocampus of 1-BP-exposed rats. These results demonstrate that subchronic inhalation exposure to 1-BP vapor reduces the function of the hippocampal GABAergic system, which could be due to changes in the expression and function of GABAA receptors, especially the delta subunit-containing GABAA receptors.

Animals↗
PubMed2006

Carboxyl-terminal splicing enhances physical interactions between the cytoplasmic tails of purinergic P2X receptors.

Purinergic P2X receptors are ion-conducting channels composed of three subunits, each having two transmembrane domains and intracellular amino (N) and carboxyl (C) termini. Although alternative splicing extensively modifies the C-terminal sequences of P2X subunits, the direct influence of such post-transcriptional modifications on receptor architecture and function remains poorly understood. In this study, we focused on mouse pituitary P2X2 receptors. In this tissue, progressive splicing of the P2X2a C terminus generated two functional subunit variants, P2X2b and P2X2e, which exhibited accelerated desensitization rates and attenuated calcium signals when the receptors were in homomeric states. To measure the intersubunit interaction in living cells, the efficient transfer of bioluminescent resonance energy between luciferase and fluorescent proteins attached to the N- or C-subunit termini of these subunits was used. The constitutive interactions between the full-length C termini of P2X2a receptor were detected by a significant increase in fluorescence/luminescence intensity ratio compared with negative controls. Moreover, interactions between C termini and between C- and N termini of adjacent subunits were significantly enhanced in homomeric and heteromeric receptors containing P2X2b or P2X2e subunits. Finally, deletion of two amino acids at the splicing junction, but not at the C-terminal end of the P2X2b receptor, resulted in the enhancement of channel desensitization and luminescence resonance energy transfer. These results indicate that C-terminal structure plays a critical role in the cytoplasmic intersubunit interactions and suggest that the extent of subunit interactions before ATP application could contribute to the subsequent channel activity and conformation changes associated with agonist-dependent desensitization.

Adenosine Triphosphate↗
PubMed2005

Stimulation of catecholamine synthesis through unique estrogen receptors in the bovine adrenomedullary plasma membrane by 17beta-estradiol.

Incubation of cultured bovine adrenal medullary cells with 17beta-estradiol (E(2)) (0.3-100nM) or membrane-impermeable E(2)-bovine serum albumin (100nM) acutely increased (14)C-catecholamine synthesis from [(14)C]tyrosine. The stimulatory effect of E(2) was not inhibited by ICI182,780, a nuclear estrogen receptor inhibitor. E(2) also increased tyrosine hydroxylase activity and p44/42MAPK phosphorylation, the former of which was attenuated by U0126, an inhibitor of p44/42MAPK kinase. The plasma membrane isolated from the gland showed two classes of specific binding sites of [(3)H]E(2) with apparent K(d)s of 3.2 and 106nM, and B(max)s of 0.44 and 8.5pmol/mg protein, respectively. The high-affinity binding of [(3)H]E(2) was most strongly inhibited by E(2) and phytoestrogens, and to lesser extents by other steroid hormones, while it was enhanced by ICI182,780 and environmental estrogenic pollutants. These findings suggest that E(2) acutely stimulates catecholamine synthesis via activation of p44/42MAPK through unique estrogen receptors in the plasma membrane of bovine adrenal medulla.

Adrenal Medulla↗
PubMed2005

Effect of prolonged exposure to milnacipran on norepinephrine transporter in cultured bovine adrenal medullary cells.

The antidepressants milnacipran and paroxetine are used clinically worldwide. In the present study, we report here the effects of treatment with milnacipran and paroxetine on the functional activity, binding sites, and mRNA of the norepinephrine (NE) transporter (NET) in cultured bovine adrenal medullary cells. In acute treatment with antidepressants for 20 min, both milnacipran and paroxetine competitively inhibited NET function in cultured adrenal medullary cells. Prolonged treatment of adrenal medullary cells with milnacipran produced time (48-96h)- and concentration (35-355 nM)-dependent increases in [3H]NE uptake and [3H]DMI binding without any increase in NET mRNA. At a high concentration (800 nM, 72 h), paroxetine suppressed [3H]NE uptake. To examine whether milnacipran-induced [3H]NE uptake is mediated by newly synthesized mRNAs or proteins, we used actinomycin D, an inhibitor of DNA-dependent RNA polymerase, and cycloheximide, an inhibitor of ribosomal protein synthesis. Cycloheximide (1 micorM, 72 h) abolished the effect of milnacipran on [3H]NE uptake, while the stimulatory effect of milnacipran was observed in actinomycin D-treated cells. The present findings suggest that prolonged exposure to milnacipran up-regulates the NET function, probably through a post-transcriptional process of NET or other proteins.

Adrenal Medulla↗
PubMed2005

Vascular neuronal NO synthase is selectively upregulated by platelet-derived growth factor: involvement of the MEK/ERK pathway.

OBJECTIVE: We demonstrated recently that neuronal NO synthase (NOS) is expressed in arteriosclerotic lesions and exerts important vasculoprotective effects in vivo. In this study, we examined the molecular mechanism(s) for vascular neuronal NOS (nNOS) expression. METHODS AND RESULTS: In cultured rat aortic smooth muscle cells, treatment with platelet-derived growth factor (PDGF) selectively upregulated nNOS expression but not inducible NOS (iNOS) or endothelial NOS (eNOS) expression. Treatment with PDGF also significantly caused activation of mitogen-activated protein kinase (MAPK) family, including extracellular signal-regulated kinase (ERK), p38MAPK, and c-Jun N-terminal kinase (JNK). ERK kinase (MAPK kinase [MEK]) inhibitors inhibited PDGF-induced nNOS expression, whereas a p38MAPK inhibitor or JNK inhibitor was without effects. Importantly, gene transfer of MEK per se elicited nNOS induction, and gene transfer of dominant-negative MEK abolished PDGF-induced nNOS expression. In isolated aortas of wild-type, eNOS(-/-), and iNOS(-/-) mice, but not in those of nNOS(-/-) mice, treatment with PDGF significantly enhanced nNOS expression and nitrite plus nitrate production, both of which were again attenuated by a MEK inhibitor. CONCLUSIONS: These results provide the first evidence that vascular nNOS expression is upregulated selectively in response to PDGF through the MEK/ERK pathway. Upregulated nNOS may play an important compensatory role under arteriosclerotic/inflammatory conditions associated with eNOS dysfunction to maintain vascular homeostasis.

Angiotensin II↗
PubMed2005

Intracellular cAMP controls a physical association of V-1 with CapZ in cultured mammalian endocrine cells.

V-1, an ankyrin repeat protein with the activity to control tyrosine hydroxylase (TH) gene expression and transmitter release in PC12D cells, associates with CapZ, an actin capping protein, and thereby regulates actin polymerization in vitro. In this study, immunoprecipitation and Western blot analysis showed that V-1 was physically associated with CapZ-beta in PC12D transfectants overexpressing V-1. These proteins were co-localized in the soma of Purkinje cells of rat cerebellum as assayed by immunohistochemistry. Furthermore, in the V-1 transfectants, the amount of CapZ which physically associated with V-1 was steeply reduced at 2h after treatment with forskolin, but was thereafter increased to reach its initial level at 12h after forskolin-treatment. These results suggest that the association of V-1 with CapZ is controlled by a cAMP-dependent signalling pathway probably to play a functional role in the regulatory mechanism of actin dynamics in the endocrine system and the central nervous system.

Adrenal Medulla↗
PubMed2005

Selective blockade of nicotinic acetylcholine receptors by pimobendan, a drug for the treatment of heart failure: reduction of catecholamine secretion and synthesis in adrenal medullary cells.

Pimobendan, a Ca(2+) sensitizer, is used clinically in the treatment of chronic heart failure. Although chronic heart failure is associated with activation of the sympathetic nervous system, it remains unknown whether pimobendan affects the function of sympathetic neurons and the adrenal medulla. Here, we report the inhibitory effects of pimobendan on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. Pimobendan decreased the catecholamine secretion (IC(50)=29.5 microM) elicited by carbachol, an agonist at nicotinic acetylcholine receptors, but not that elicited by veratridine, an activator of voltage-dependent Na(+) channels, or by high K(+), an activator of voltage-dependent Ca(2+) channels. Pimobendan also inhibited carbachol-induced influx of (22)Na(+) (IC(50)=25.9 microM) and (45)Ca(2+) (IC(50)=26.0 microM), but not veratridine-induced (22)Na(+) influx or high K(+)-induced (45)Ca(2+) influx. The reduction of catecholamine secretion caused by pimobendan was not overcome by increasing the concentration of carbachol. UD-CG 212, an active metabolite of pimobendan, lowered carbachol-induced catecholamine secretion with a concentration/inhibition curve similar to that of pimobendan. In experiments in situ, pimobendan suppressed both basal and carbachol-stimulated (14)C-catecholamine synthesis (IC(50)=5.3 and 4.9 microM) from [(14)C] tyrosine [but not from L: -3, 4-dihydroxyphenyl [3-(14)C] alanine ([(14)C]DOPA)], as well as tyrosine hydroxylase activity (IC(50)=3.8 and 4.3 microM). These findings suggest that pimobendan inhibits carbachol-induced catecholamines secretion and synthesis through suppression of nicotinic acetylcholine receptors.

Adrenal Medulla↗
PubMed2005

Effects of zotepine and olanzapine on noradrenaline transporter in cultured bovine adrenal medullary cells.

BACKGROUND: Previously, it was demonstrated that the inhibitory effects of atypical antipsychotic drugs such as clozapine and risperidone on noradrenaline transporter (NAT) might in part be associated with their clinical profile. The present study examined the effects of zotepine on NAT in the cells and compared them with those of olanzapine. MATERIALS AND METHODS: Adrenal medullary cells were isolated by a method of collagenase digestion of slices of fresh bovine adrenal medulla and the cells were plated at a density of 4 x 10(6) cells. Cells were incubated with [3H]noradrenaline (NA) in the presence or absence of zotepine or olanzapine. The amount of radioactivity taken into the cells was counted by a liquid scintillation counter. Plasma membranes of bovine adrenal medulla were prepared, and the binding of [3H]desipramine (DMI) was determined by incubating the membrane suspension in binding buffer together with zotepine or olanzapine. Specific binding of [3H] DMI was defined as that binding which was inhibited by nisoxetine. RESULTS: Both zotepine (10-1000 ng/ml) and olanzapine (10-1000 ng/ml) decreased [3H]NA uptake in a concentration-dependent manner. The IC50 values of zotepine and olanzapine on [3H]NA uptake were 10 +/- 4 and 14 +/- 8 ng/ml, respectively. Eadie-Hofstee analysis of [3H]NA uptake showed that treatment with zotepine and olanzapine decreased the V(max) of uptake without changing the K(m). Both zotepine (10-1000 ng/ml) and olanzapine (30-1000 ng/ml) inhibited [3H]DMI binding in a concentration-dependent manner. The IC50 values of zotepine and olanzapine on [3H]DMI binding were 50 +/- 18, and 120 +/- 38 ng/ml, respectively. Scatchard plot analysis of [3H]DMI binding showed that zotepine and olanzapine decreased the B(max) of binding without altering the K(d). CONCLUSIONS: The inhibitory effects of zotepine and olanzapine might be responsible in part for their clinical profile.

Adrenal Medulla↗
PubMed2004

Stimulation of catecholamine synthesis by environmental estrogenic pollutants.

Environmental estrogenic pollutants are compounds that have been shown to have estrogenic effects on fetal development and reproductive systems. Less attention, however, has been paid to their influence on neuronal functions. We report here the effects of estrogenic pollutants on catecholamine synthesis in bovine adrenal medullary cells used as a model system of noradrenergic neurons. Treatment of cultured bovine adrenal medullary cells with p-nonylphenol and bisphenol A at 10 nM for 3 d stimulated [14C]catecholamine synthesis from [14C]tyrosine and tyrosine hydroxylase activity, an effect that was not inhibited by ICI 182,780, an antagonist of estrogen receptors. Significant effects of p-nonylphenol on [14C]catecholamine synthesis were observed at 0.1 nM, which is 45 times lower than that of the international regulatory standard (4.5 nM), and the maximum effects were around 10-100 nM. The concentrations (0.1-10 nM) used in the present study are similar to the range observed in rivers in the United States or Europe. On the other hand, short-term treatment of cells with 10 nM p-nonylphenol for 10 min also activated tyrosine hydroxylase, which was suppressed by U0126, an inhibitor of MAPK kinase. Furthermore, treatment of cells with p-nonylphenol for 5 min increased the phospho-p44/42MAPK in a concentration-dependent (1-1000 nM) manner, whereas p-nonylphenol (100 nm, 2 d) enhanced both levels of non-phospho- and phospho-p44/42MAPK. These findings suggest that short-term and long-term treatment of cells with estrogenic pollutants at environmental concentrations stimulates catecholamine synthesis and MAPK through an estrogen receptor-independent pathway.

Adrenal Medulla↗
PubMed2004

Asymmetric dimethylarginine produces vascular lesions in endothelial nitric oxide synthase-deficient mice: involvement of renin-angiotensin system and oxidative stress.

OBJECTIVE: Asymmetric dimethylarginine (ADMA) is widely believed to be an endogenous nitric oxide synthase (eNOS) inhibitor. However, in this study, we examined our hypothesis that the long-term vascular effects of ADMA are not mediated by inhibition of endothelial NO synthesis. METHODS AND RESULTS: ADMA was infused in wild-type and eNOS-knockout (KO) mice by osmotic minipump for 4 weeks. In wild-type mice, long-term treatment with ADMA caused significant coronary microvascular lesions. Importantly, in eNOS-KO mice, treatment with ADMA also caused an extent of coronary microvascular lesions that was comparable to that in wild-type mice. These vascular effects of ADMA were not prevented by supplementation of l-arginine, and vascular NO production was not reduced by ADMA treatment. Treatment with ADMA caused upregulation of angiotensin-converting enzyme (ACE) and an increase in superoxide production that were comparable in both strains and that were abolished by simultaneous treatment with temocapril (ACE inhibitor) or olmesartan (AT(1) receptor antagonist), which simultaneously suppressed vascular lesion formation. CONCLUSIONS: These results provide the first direct evidence that the long-term vascular effects of ADMA are not solely mediated by simple inhibition of endothelial NO synthesis. Direct upregulation of ACE and increased oxidative stress through AT(1) receptor appear to be involved in the long-term vascular effects of ADMA in vivo. This study demonstrates that asymmetrical dimethylarginine (ADMA) causes arteriosclerotic coronary lesions in mice in vivo through mechanisms other than simple inhibition of endothelial NO synthesis. Our findings should contribute to a better understanding of the pathophysiological role of ADMA in arteriosclerosis.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2004

Sites of positive allosteric modulation by neurosteroids on ionotropic gamma-aminobutyric acid receptor subunits.

Neurosteroids are known as allosteric modulators of ionotropic gamma-aminobutyric acid (GABA) receptors. Here, we investigated sites of positive allosteric modulation by allotetrahydrodeoxycorticosterone (5alpha-THDOC) at GABA receptors using the technique of chimeragenesis and the Xenopus oocyte expression system. Our findings have demonstrated that the region from transmembrane segment (TM) 4 to the C-terminus of the GABA(A) receptor alpha1 subunit is crucial for the action of 5alpha-THDOC, but insufficient for the action of another neurosteroid allopregnanolone, suggesting that a specific region critical for neurosteroid action at GABA receptors exists in the domain between TM4 and the C-terminus of GABA receptor subunits.

Allosteric Regulation↗
PubMed2003

Stimulation of catecholamine synthesis by orexin-A in bovine adrenal medullary cells through orexin receptor 1.

Orexin-A has recently been identified as a new hypothalamic peptide working as a mediator in the regulation of feeding behavior and sleep control. To determine the role of orexin-A in peripheral metabolic processes, we examined direct effects of orexin-A on catecholamine synthesis and secretion in cultured bovine adrenal medullary cells. Incubation of cells with orexin-A (100 pM) for 20 min caused a small but significant increase in 14C-catecholamine synthesis from [14C]tyrosine, but not from L-3,4-dihydroxyphenyl[3-14C]alanine. Orexin-A (100 pM) potentiated the stimulatory effects of acetylcholine (0.3 mM) on 14C-catecholamine synthesis. Orexin-A significantly increased tyrosine hydroxylase activity, which was evident at 1 pM and maximal at 100 pM. 4 beta-Phorbol-12 beta-myristate-13 alpha-acetate, an activator of protein kinase C, did not enhance the stimulatory effects of orexin-A on tyrosine hydroxylase activity, while H-7 and staurosporine, inhibitors of protein kinase C, nullified the effects of orexin-A. Orexin-A had little effect on catecholamine secretion from the cells. Orexin receptor 1 (OX(1)R) but not orexin receptor 2 (OX(2)R) mRNA was detected in bovine adrenal medullary cells by reverse transcriptase-polymerase chain reaction. These findings suggest that orexin-A activates tyrosine hydroxylase and then stimulates catecholamine synthesis, probably via activation of the OX(1)R-protein kinase C pathway in adrenal medullary cells.

Acetylcholine↗
PubMed2003

Inhibition of the norepinephrine transporter function in cultured bovine adrenal medullary cells by bisphenol A.

We report here the effects of an environmental estrogen, bisphenol A, on norepinephrine (NE) transporter function in cultured bovine adrenal medullary cells. The effects of bisphenol A were compared to those of 17beta-estradiol. Bisphenol A significantly inhibited [3H]NE uptake by the cells in a concentration-dependent manner (1-100 microM). Kinetic analysis revealed that bisphenol A, as well as 17beta-estradiol, noncompetitively inhibited [3H]NE uptake. Bisphenol A and 17beta-estradiol inhibited the specific binding of [3H]desipramine to plasma membranes isolated from bovine adrenal medulla. As shown by Scatchard analysis of [3H]desipramine binding, bisphenol A increased the dissociation constant (K(d)) and decreased the maximal binding (B(max)), indicating a mixed type of inhibition. 17beta-Estradiol increased the K(d) without altering the B(max), thereby indicating competitive inhibition. The present findings suggest that bisphenol A inhibits the function of the NE transporter by acting on a site different from that of 17beta-estradiol in the adrenal medulla and probably in the brain noradrenergic neurons.

Adrenal Medulla↗
PubMed2002

Heteromultimerization modulates P2X receptor functions through participating extracellular and C-terminal subdomains.

P2X purinergic receptors (P2XRs) differ among themselves with respect to their ligand preferences and channel kinetics during activation, desensitization, and recovery. However, the contributions of distinct receptor subdomains to the subtype-specific behavior have been incompletely characterized. Here we show that homomeric receptors having the extracellular domain of the P2X(3) subunit in the P2X(2a)-based backbone (P2X(2a)/X(3)ex) mimicked two intrinsic functions of P2X(3)R, sensitivity to alphabeta-methylene ATP and ecto-ATPase-dependent recovery from endogenous desensitization; these two functions were localized to the N- and C-terminal halves of the P2X(3) extracellular loop, respectively. The chimeric P2X(2a)R/X(3)ex receptors also desensitized with accelerated rates compared with native P2X(2a)R, and the introduction of P2X(2) C-terminal splicing into the chimeric subunit (P2X(2b)/X(3)ex) further increased the rate of desensitization. Physical and functional heteromerization of native P2X(2a) and P2X(2b) subunits was also demonstrated. In heteromeric receptors, the ectodomain of P2X(3) was a structural determinant for ligand selectivity and recovery from desensitization, and the C terminus of P2X(2) was an important factor for the desensitization rate. Furthermore, [gamma-(32)P]8-azido ATP, a photoreactive agonist, was effectively cross-linked to P2X(3) subunit in homomeric receptors but not in heteromeric P2X(2) + P2X(3)Rs. These results indicate that heteromeric receptors formed by distinct P2XR subunits develop new functions resulting from integrative effects of the participating extracellular and C-terminal subdomains.

Adenosine Triphosphatases↗
PubMed2002

Glucocorticoid inhibits expression of V-1, a catecholamine biosynthesis regulatory protein, in cultured adrenal medullary cells.

V-1 acts as a positive and coordinate regulator of gene expression of catecholamine biosynthetic enzymes in PC12D cells. The present study was conducted to investigate the mechanism controlling expression of V-1 in the adrenal gland. Immunohistochemical analysis demonstrated that noradrenergic chromaffin cells more highly expressed V-1 than adrenergic chromaffin cells preferentially expressing the glucocorticoid receptor in rat adrenal glands. Western blotting showed that in cultured bovine adrenal medullary cells, dexamethasone, a synthetic glucocorticoid, inhibited expression of V-1, and that this inhibition was prevented by RU-486, a glucocorticoid receptor antagonist. These results suggest that adrenal expression of V-1 is differentially controlled by glucocorticoids through the specific receptor, and that thereby V-1 regulates catecholamine biosynthesis in a catecholaminergic phenotype-dependent manner.

Adrenal Medulla↗