Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dietary protein independently modulates albuminuria (U(Alb)V) and albumin synthesis (AlbSyn) in nephrotic rats. While some amino acids are without effect on renal hemodynamics, arginine (Arg) augments renal blood flow and glomerular filtration rate, increases AlbSyn in tissue culture and isolated perfused livers, and could be one specific amino acid causing both decreased glomerular permselectivity and increased AlbSyn. Nephrotic rats were fed 10% casein (LP); 30% casein (HP); 30% casein with the inhibitor of nitric oxide (NO) synthesis N omega-nitro-L-arginine methyl ester (HP + L-NAME); 10% casein supplemented with Arg and amino acids that are Arg precursors of or are derived from Arg (proline, glutamate, and aspartate) in an amount in the increment between 10 and 30% casein (ArgAA); ArgAA supplemented with NH4 acetate to provide a diet isonitrogenous to 30% casein (ArgAA + NH4); or 10% casein plus an incomplete mixture of amino acids (Inc) containing the increment in histidine, phenylalanine, tryptophan, tyrosine, lysine, glycine, alanine, serine, threonine, cysteine, and methionine provided when the diet was changed from 10 to 30% casein. U(Alb)V increased significantly in HP and by a significantly greater amount in HP + L-NAME, but did not change in LP, ArgAA, or ArgAA + NH4. U(Alb)V tended to increase in Inc, was significantly greater than in LP or in ArgAA + NH4, but less than in HP. AlbSyn ([3H]phenylalanine incorporation) was no different in Inc than in HP, and was significantly greater than in either ArgAA + NH4 or LP. Increased AlbSyn results from increased ingestion of one or more of amino acids in Inc, but not from Arg or its precursors or products or from total dietary nitrogen.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Arginine augments neither albuminuria nor albumin synthesis caused by high-protein diets in nephrosis. 144 79

We have identified two types of polymorphism at the CAR (cell adhesion regulator) locus. One is a conventional TaqI polymorphism and the other is an insertion/deletion polymorphism in the coding region. One has the nucleotide sequence AGTGAGGCA (Ser-Gln-Ala) at nt 271-279, whereas the variant has ACAC-AGTGAGGCCCA (Thr-Gln-Ser-Gly-Pro). Although it is not clear whether this variation of amino acids affects the biological function of the gene product, this variant was detected in nine chromosomes among 30 unrelated Japanese individuals. Genetic linkage analysis based on the genotypes of TaqI polymorphism in CEPH families revealed close linkage of CAR to D16S7 and D16S154, which are located in the peritelomeric region of the long arm of chromosome 16.
 ...
PMID:The cell adhesion regulator (CAR) gene, TaqI and insertion/deletion polymorphisms, and regional assignment to the peritelomeric region of 16q by linkage analysis. 809 8

Perfusion with ([N-Me-Phe3,D-Pro4]morphiceptin (PL017)), [D-Pen2,5]enkephalin (DPDPE) and MEt5 and Leu5 enkephalin induced circular muscle contractions and decreased immunoreactive vasoactive intestinal polypeptide (VIP) venous output in canine ileal segments. Motility and VIP responses to PL017 were abolished by the mu antagonist CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2) and unchanged by the delta antagonist ICI 174,864 ([N,N-dially-Tyr1,Aib2,3]Leu-enkephalin) which abolished DPDPE motility and VIP responses. The VIP response to DPDPE was unchanged by CTAP, which reduced motility responses, suggesting a DPDPE interaction with endogenous mu opioids, at a mu/delta(complexed) receptor. ICI 174,864 abolished Met5 and Leu5 enkephalin motility responses and Leu5 enkephalin VIP responses while CTAP was ineffective on Leu5 enkephalin motility responses or on both enkephalin VIP responses. CTAP increased Met5 enkephalin motility responses suggesting mu actions to inhibit excitatory nerves. ICI 174,864 reduced Met5 enkephalin VIP output decrements requiring CTAP addition for abolition, suggesting actions at mu/delta(complexed) receptors. Inhibition of nitric oxide synthase with N-omega-L-arginine methyl ester (L-NAME) abolished delta opioid and reduced by 30% mu opioid motility responses, leaving the VIP response intact. Hexamethonium and atropine abolished tonic VIP output, leaving intact motility responses to PL017 and DPDPE. Subsequently L-NAME eliminated delta opioid and reduced by 1/3 mu opioid motility responses. All opioids reduced the NO-mediated IJPs in myenteric plexus-free ileal circular muscle. Thus mu or delta opioids inhibit both NO and VIP release but removal of NO, not VIP, disinhibits circular muscle motility.
 ...
PMID:Identification of mechanisms and sites of actions of mu and delta opioid receptor activation in the canine intestine. 811 80

The heptapeptide, angiotensin-(1-7), is an active member of the renin-angiotensin system. The present study was designed to characterize the role of endothelium in relaxations of large cerebral arteries to angiotensin-(1-7). Rings of canine middle cerebral arteries were suspended in organ chambers for isometric force recording. The levels of cyclic guanosine 3',5'-monophosphate (cGMP) were assessed by radioimmunoassay. During contraction to uridine 5'-triphosphate (UTP, 3x10(-6) to 10(-5) mol/l), angiotensin-(1-7) (10(-9) to 3x10(-5) mol/l) caused concentration-dependent relaxations in arteries with endothelium, but not in endothelium-denuded vessels. Angiotensin-(1-7) significantly increased formation of cGMP. Nitric oxide synthase inhibitor, N-omega-nitro-L-arginine methyl ester (L-NAME, 3x10(-4) mol/l), and selective soluble guanylate cyclase inhibitor, 1 H-[1,2, 4]oxadiazolo[4,3-a]quinozalin-1-one (ODQ, 3x10(-6) mol/l), abolished angiotensin-(1-7)-induced relaxations. Angiotensin receptor antagonists, losartan (10(-5) mol/l), PD 123319 (10(-5) mol/l), [Sar(1),Thr(8)]-angiotensin II (10(-5) mol/l) [Sar(1),Val(5), Ala(8)]-angiotensin II (10(-5) mol/l) or [7-D-Ala]-angiotensin 1-7 (10(-6) mol/l) did not affect these relaxations. However, angiotensin-converting enzyme inhibitor, captopril (10(-5) mol/l) augmented relaxations to angiotensin-(1-7). Finally, bradykinin B(2) receptor antagonist, [D-Arg(0),Hyp(3),Thi(5),D-Tic(7), Oic(8)]-bradykinin (HOE 140, 5x10(-8) mol/l) significantly reduced the effect of angiotensin-(1-7), while bradykinin B(1) receptor antagonist, des-Arg(9), [Leu(8)]-bradykinin (6x10(-9) mol/l) did not influence the vascular response to the heptapeptide. These findings indicate that (1) angiotensin-(1-7) produces relaxation of canine middle cerebral arteries by the release of nitric oxide from endothelial cells, (2) angiotensin receptors do not mediate endothelium-dependent relaxations to the heptapeptide, and (3) this effect appears to be dependent on activation of local production of kinins. Our studies support the concept that angiotensin-(1-7), as a natural vasodilator hormone, may counterbalance the hemodynamic actions of angiotensin II.
 ...
PMID:Angiotensin-(1-7) causes endothelium-dependent relaxation in canine middle cerebral artery. 1091 12

Steroid hormones modulate activity of the nuclear receptor constitutive active receptor (CAR, or constitutive androstane receptor) in mouse liver. Progesterone and testosterone repress the constitutive activity of mouse CAR (mCAR) in cell-mediated transfection assays, whereas estrogens activate the repressed receptor. This repression and activation is not observed with human CAR. To define the structural basis that confers the hormone responsiveness to mCAR, we constructed various chimeric and mutated receptors and examined their response to steroid hormones. The hormone responsiveness resided near or within AF-2 domain of mCAR. Moreover, a single mutation of threonine at position 350 to the corresponding methionine in the human counterpart abolished the repression of mCAR by steroid hormones. Coactivation by steroid receptor coactivator 1 (SRC-1) of mCAR did not depend on the threonine 350. However, overexpression of SRC-1 counteracted progesterone to repress mCAR activity. Thus, threonine 350 seems to regulate hormone responsiveness of mCAR by interfering indirectly an interaction of the receptor with a coactivator.
 ...
PMID:Residue threonine 350 confers steroid hormone responsiveness to the mouse nuclear orphan receptor CAR. 1202 88

Reactive oxygen species (superoxide anion, hydrogen peroxide, and nitric oxide) are involved in human sperm capacitation and associated tyrosine (Tyr) phosphorylation through a cAMP- and protein kinase A-mediated pathway. Recently, we evidenced the double phosphorylation of the threonine-glutamine-Tyr motif (P-Thr-Glu-Tyr-P) in human sperm proteins of 80 and 105 kDa during capacitation. The objective of the present study was to investigate the role of reactive oxygen species in the regulation of this process and to immunolocalize the P-Thr-Glu-Tyr-P motif in human spermatozoa. Superoxide dismutase and catalase did not prevent, and exogenous addition of superoxide anion or hydrogen peroxide did not trigger, the increase in P-Thr-Glu-Tyr-P related to sperm capacitation. However, l-NAME (a competitive inhibitor of l-arginine for nitric oxide synthase) prevented, and a nitric oxide donor promoted, the increase in P-Thr-Glu-Tyr-P related to sperm capacitation. In addition, l-arginine reversed the inhibitory effect of l-NAME on capacitation and the associated increase of P-Thr-Glu-Tyr-P. Therefore, the regulation of P-Thr-Glu-Tyr-P is specific to nitric oxide and not to superoxide anion or hydrogen peroxide. The nitric oxide-mediated increase of P-Thr-Glu-Tyr-P involved protein Tyr kinase, MEK or MEK-like kinase, and protein kinase C but not protein kinase A. The P-Thr-Glu-Tyr-P motif was immunolocalized to the principal piece region of spermatozoa. In conclusion, nitric oxide regulates the level of P-Thr-Glu-Tyr-P in sperm proteins of 80 and 105 kDa during capacitation. These data evidence, to our knowledge for the first time, a specific role for nitric oxide in signal transduction events leading to sperm capacitation.
 ...
PMID:Nitric oxide regulates the phosphorylation of the threonine-glutamine-tyrosine motif in proteins of human spermatozoa during capacitation. 1260 10

The effects of somatostatin on blood flow, plasma extravasation and knee joint sizes in the rat were investigated. Topical bolus administrations of somatostatin (10 pmol-100 nmol) onto the exposed rat knee joint capsules produced dose-dependent increases in knee joint blood flow with an ED(50) value of 1.7 nmol, and a maximum increase of 109.7%. The peak vasodilator response was observed at 1 min following drug administration, and it subsided at 5 min. Treatment of the rat knee with a somatostatin receptor antagonist cyclo(7-aminoheptanoul-Phe-D-Trp-Lys-Thr[Bzl] (cyclo-somatostatin; 2 x 20 nmol) significantly suppressed the somatostatin-induced vasodilator response, but treatment with the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME; 2 x 50 nmol) or the cyclo-oxygenase inhibitor flurbiprofen (2 x 10 nmol) had no effect. Unilateral intraarticular injections of somatostatin (10 nmol) produced no change on blood flow and sizes of the rat knee joints, but elicited marked ipsilateral Evans blue extravasation. Cyclo-somatostatin at doses of 2 x 20 and 2 x 50 nmol did not affect the plasma extravasation response to somatostatin. The present findings indicate the vasodilator effect of somatostatin is mediated by receptors sensitive to cyclo-somatostatin inhibition, but its plasma extravasation effect might be mediated by somatostatin receptor types that are resistant to inhibition by cyclo-somatostatin. There is no evidence that nitric oxide and prostaglandins are involved in the somatostatin-induced vasodilator response. It is suspected that the vascular effects of somatostatin demonstrated in this study would play a part in the innate response of an inflammatory reaction.
 ...
PMID:Characterisation of somatostatin actions on knee joint blood vessels of the rat. 1292 76

Lactoferrin (LF) is a multifunctional protein found in various biological fluids. However, the peripheral action of lactoferrin remains unknown. In this study, peripherally applied bovine lactoferrin showed antinociceptive effect that was reversed by a mu-opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-NH(2) (CTOP), or by a nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), but not by an inactive enantiomer of L-NAME, N(G)-nitro-D-arginine methyl ester (D-NAME), during phase 1 and phase 2 in the rat formalin test. Peripheral coadministration of a micro-opioid receptor agonist, morphine, with subeffective dose of bovine lactoferrin produced a potentiated antinociceptive effect compared to that of morphine alone during both phases in the formalin test. This potentiated antinociception by morphine with bovine lactoferrin was reversed by CTOP or by L-NAME. These results suggest that bovine lactoferrin exerts an antinociceptive activity via potentiation of the peripheral micro-opioidergic system, and that nitric oxide (NO) is involved in this potentiation.
 ...
PMID:Lactoferrin enhances peripheral opioid-mediated antinociception via nitric oxide in rats. 1474 1

AMP-activated protein kinase (AMPK) independently increases glucose and long-chain fatty acid (LCFA) utilization in isolated cardiac muscle preparations. Recent studies indicate this may be due to AMPK-induced phosphorylation and activation of nitric oxide synthase (NOS). Given this, the aim of the present study was to assess the effects of AMPK stimulation by 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR; 10 mg.kg(-1).min(-1)) on glucose and LCFA utilization in cardiac muscle and to determine the NOS dependence of any observed effects. Catheters were chronically implanted in a carotid artery and jugular vein of Sprague-Dawley rats. After 4 days of recovery, conscious, unrestrained rats were given either water or water containing 1 mg/ml nitro-L-arginine methyl ester (L-NAME) for 2.5 days. After an overnight fast, rats underwent one of four protocols: saline, AICAR, AICAR + L-NAME, or AICAR + Intralipid (20%, 0.02 ml.kg(-1).min(-1)). Glucose was clamped at approximately 6.5 mM in all groups, and an intravenous bolus of 2-deoxy-[(3)H]glucose and [(125)I]-15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid was administered to obtain indexes of glucose and LCFA uptake and clearance. Despite AMPK activation, as evidenced by acetyl-CoA carboxylase (Ser(221)) and AMPK phosphorylation (Thr(172)), AICAR increased cardiac LCFA but not glucose clearance. L-NAME + AICAR established that this effect was not due to NOS activation, and AICAR + Intralipid showed that increased cardiac LCFA clearance was not LCFA-concentration dependent. These results demonstrate that, in vivo, AMPK stimulation increases LCFA but not glucose clearance by a NOS-independent mechanism.
 ...
PMID:AMPK stimulation increases LCFA but not glucose clearance in cardiac muscle in vivo. 1526 60

The mouse nuclear receptor CAR (constitutively active receptor) is a transcription factor that is activated by phenobarbital-type inducers such as TCPOBOP {1,4 bis[2-(3,5-dichloropyridyloxy)]benzene} in liver in vivo. However, CAR is constitutively active in cell-based transfection assays, the molecular mechanism for which has not been elucidated yet. In the model structure of CAR, Thr176 constitutes a part of the ligand-binding surface, but its side chain is not directed toward the surface, instead it forms a hydrogen bond with Thr350 in the AF2 (activation function 2) domain of CAR. Thr350 is known to regulate CAR activity [Ueda, Kakizaki, Negishi, and Sueyoshi (2002) Mol. Pharmacol. 61, 1284-1288]. Thr176 was mutated to various amino acids to examine whether this interaction played a role in conferring the constitutive activity. Hydrophobic and positively charged amino acids at position 176 abrogated the constitutive activity, whereas polar and negatively charged amino acids retained it. When one of the small hydrophobic amino acids, such as alanine or valine, was substituted for threonine, the mutants were fully activated by TCPOBOP. The co-activator SRC-1 (steroid receptor co-activator-1) regulated the activity changes associated with the mutations. Thr248 and Ser230 are the Thr176-corresponding residues in human pregnane X receptor and mouse vitamin D3 receptor respectively, interacting directly with the conserved threonine in the AF2 domains. Thr248 and Ser230 also regulated the ligand-dependent activity of these receptors by augmenting binding of the receptors to SRC-1. Thr176, Thr248 and Ser230 are conserved residues in the NR1I (nuclear receptor 1I) subfamily members and determine their activity.
 ...
PMID:Thr176 regulates the activity of the mouse nuclear receptor CAR and is conserved in the NR1I subfamily members PXR and VDR. 1561 65


1 2 3 4 5 Next >>