Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of selective opioid receptor agonists and antagonists on neural discharge recorded from carotid body arterial chemoreceptors in vivo were studied in anaesthetized cats. Mean ID50 values were determined for each agonist and used to assess chemodepressant potency on intracarotid (i.c.) injection in animals artificially ventilated with air. [Met]enkephalin, [Leu]enkephalin, [D-Ala2, D-Leu5]enkephalin and [D-Pen2, D-Pen5]enkephalin were more potent chemodepressants than [D-Ala2, Me-Phe4, Gly-ol5]enkephalin, dynorphin (1-8) or ethylketocyclazocine; morphiceptin (mu-agonist) was inactive. The rank order of potency was compatible with the involvement of delta-opioid receptors in opioid-induced depression of chemosensory discharge. ICI 154129, a delta-opioid receptor antagonist, was used in fairly high doses and caused reversible dose-related antagonism of chemodepression induced by [Met]enkephalin. It also antagonized depression caused by single doses of [Leu]enkephalin, [D-Ala2, D-Leu5]enkephalin, [D-Ala2, Me-Phe4, Gly-ol5]enkephalin or dynorphin (1-8). ICI 174864, a more potent and selective delta-opioid receptor antagonist, also antagonized chemodepression induced by [Met]enkephalin or by the selective delta-receptor agonist [D-Pen2, D-Pen5]enkephalin. Comparison of background or 'spontaneous' chemosensory discharge during the 30 min periods immediately before and after injecting ICI 174864 (0.1-0.2 mg kg-1 i.c.) showed a significant increase in discharge in one experiment, but in four others discharge was either unaffected or decreased after the antagonist, which argues against a toxic depression of chemosensors by endogenous opioids under resting conditions in our preparation. Sensitivity of the carotid chemoreceptors to hypoxia (ventilating with 10% O2) was increased significantly after ICI 174864, which could be taken as evidence that endogenous opioids depress chemosensitivity during hypoxia. In contrast, responsiveness to hypercapnia was reduced after the antagonist, implying that endogenous opioids may potentiate chemoreceptor sensitivity during hypercapnia. The results obtained using 'selective' agonists and antagonists provide evidence that depression of chemosensory discharge caused by injected opioids involves a delta type of opioid receptor within the cat carotid body. Endogenous opioids may modulate arterial chemoreceptor sensitivity to physiological stimuli such as hypoxia and hypercapnia.
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PMID:Characterization of opioid receptors in the cat carotid body involved in chemosensory depression in vivo. 287 62

We have examined the sites phosphorylated on acetyl-CoA carboxylase by three protein kinases which have been shown to inactivate the enzyme, i.e. cyclic-AMP-dependent protein kinase, acetyl-CoA carboxylase kinase-2 (ACK2, purified from rat mammary gland) and the AMP-activated protein kinase (formerly called acetyl-CoA carboxylase kinase-3, purified from rat liver). Each protein kinase phosphorylates two out of three sites (termed 1-3) which have been established by amino acid sequencing. The two sites phosphorylated by each kinase can be recovered on separate peptides, TC1 and TC2, derived by combined digestion of the native enzyme by trypsin and chymotrypsin: TC1 = Ser-2Ser(P)-Met-3Ser(P)-Gly-Leu; TC2 = Arg-Met-1Ser(P)-Phe- Cyclic-AMP-dependent protein kinase phosphorylates sites 1 and 2 exclusively, whereas the AMP-activated protein kinase phosphorylates sites 1 and 3, plus at least one other minor site. ACK2 phosphorylates site 1 and, more slowly, an unidentified site(s) within TC1. We have also established the structures of the single major phosphopeptides (T1 and C1 respectively) which are recovered by HPLC after acetyl-CoA carboxylase phosphorylated by cyclic-AMP-dependent protein kinase is digested with trypsin or chymotrypsin alone. T1 is related to TC1, and has the structure: Ser-Ser(P)-Met-Ser-Gly-Leu-His-Leu-Val-Lys. C1 is identical with TC2. We have carried out studies on the correlation of the activity of acetyl-CoA carboxylase with the occupancy of sites 1, 2 and 3 during phosphorylation by each of the three protein kinases. The results suggest that phosphorylation of site 3 is primarily responsible for the large decrease in Vmax produced by the AMP-activated protein kinase, while phosphorylation of site 1 may be primarily responsible for the increase in A0.5 for citrate and more modest depression of Vmax produced by cyclic-AMP-dependent protein kinase and ACK2. Our results emphasize that amino acid sequence information is essential in the unequivocal interpretation of data from phosphopeptide mapping experiments and allow a more complete interpretation of previous data on phosphorylation of acetyl-CoA carboxylase in intact cells. They also open the way to experiments which could establish the physiological roles of these protein kinases in the control of fatty acid synthesis.
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PMID:Identification by amino acid sequencing of three major regulatory phosphorylation sites on rat acetyl-CoA carboxylase. 290 Jan 38

Fourteen patients with chronic aortic regurgitation (AR) underwent radionuclide angiography at rest and during supine exercise with ergometric controls. Ten subjects without evidence of heart disease were taken as controls. The behavior of heart rate, ST segment and R wave amplitude were analyzed at peak exercise in relationship with ejection fraction (EF) changes. Abnormal EF, (defined by an increase less than 10%, no change or decrease respect EF control), was present in 9 of 14 patients. Five of 14 patients had normal EF response to exercise defined by an increase of 10% or more than control value. Sensitivity and specificity of heart rate changes at exercise (abnormal: less than 10 beats to MET) to identify abnormal EF were 10% and 100%, respectively. The analysis of ST segment alterations at peak exercise (abnormal more than 2 mm ST depression) to the same objective showed 33% of sensitivity and 80% of specificity. Changes in R wave amplitude (abnormal: increase, no change or decrease less than 22% R wave amplitude at control) at peak exercise had 100% sensitivity and 80% of specificity to identify abnormal EF. Our results suggest that exercise test could be useful to analyze the response to left ventricular function during stress in patients with AR. Changes in R. wave amplitude at peak exercise appeared the best parameter.
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PMID:[Use of ergometry for evaluating left ventricular function in chronic aortic insufficiency]. 293 76

One of the leading causes of mortality in diabetics is myocardial disease. In the past few years this subject has generated a significant amount of interest with the result that myocardial problems associated with diabetes are far better understood. Though originally thought to occur as a result of atherosclerosis, various studies have shown that heart disease can occur in the absence of atherosclerosis, suggesting a diabetic cardiomyopathy. Using diabetic animals, it has been possible to characterize diabetes-induced myocardial abnormalities. Diabetic rat hearts do not respond to conditions of high stress as well as controls. The functional depression is accompanied by altered cardiac enzyme systems. A decrease in myosin ATPase activity which appears to be a result of diabetes-induced hypothyroidism is seen. Also, a depression of sarcoplasmic reticular calcium ATPase, along with a depression of calcium uptake by the SR, is seen in diabetic rat hearts. Na+, K+ ATPase activity has also been shown to be depressed and the depression appears to correlate with depressed atrial contractility. High levels of circulating fats in diabetics may alter the integrity of membranes leading to altered enzyme activities. Insulin treatment has been relatively successful at reversing or preventing myocardial changes in the diabetic rat. Other treatments that have been studied include thyroid hormone treatment, since the depression of myosin ATPase can be corrected by such treatment; and carnitine treatment, as the elevation of long chain acyl carnitines (LCAC) and the resulting depression of calcium uptake in the SR can be so normalized. These treatments have not been successful at normalizing cardiac function. A combination of the two treatments normalized function only partially, suggesting that factors besides myosin ATPase and SR calcium uptake are involved. Other treatments that have been tried include vanadate, methyl palmoxirate, and choline and methionine. Vanadate treatment has proved to be encouraging in that it normalizes both function and hyperglycemia. Methyl palmoxirate, a fatty acid analog, normalized only the elevation of LCAC but did not affect function. Methionine and choline were only partially successful in preventing the functional alterations of diabetic rat hearts. The purpose of the present article is to review our understanding of diabetes-induced myocardial problems and their possible causes. Findings from our laboratory and others are described in which attempts have been made to normalize cardiac function.
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PMID:Diabetes-induced abnormalities in the myocardium. 293 41

Systemic injection of naloxone (NAL), an opioid-receptor antagonist, significantly elevates systolic blood pressure (SBP) in anesthetized hypovolemic monkeys, providing indirect evidence that endogenous opioids contribute to cardiovascular depression during shock. The purpose of this study was to identify specific centrally located opioid receptor sites that participate in SBP regulation under normovolemic and hypovolemic conditions. In 6 monkeys, bilateral guide cannulae were stereotaxically implanted above areas ranging from the diencephalon to the lower medulla. Microinjections (1 microliter) of D- Ala2-Met-enkephalinamide (DAME) (3.4-27.2 nM) into normovolemic unanesthetized monkeys reduced SBP by 10-65 mm Hg in a dose-related fashion. Subsequent injection of NAL (12.2 nM) attenuated this hypotensive response. Heart rate fell 20-40 bpm with DAME, but not in response to dose. In the anesthetized animal rendered hypotensive (SBP = 45 mm Hg) by hemorrhage. NAL injected into predetermined DAME-sensitive sites failed to increase SBP more than 5 mm Hg. Even consecutive injections into multiple sites elevated SBP only 20 mm Hg. We conclude that the centrally located opioid-sensitive sites tested exert only a mild influence in mediating hemorrhagic hypotension.
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PMID:Effects of opiate receptor drugs injected intracerebrally into the normovolemic and hypovolemic monkey. 301 Feb 58

Intracellular recordings were made from neurons of the rat locus coeruleus contained within a brain slice maintained in vitro. When applied to the slice in known concentrations the selective kappa opioid receptor agonist trans-(+)-3,4-dichloro-N-methyl-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetamide methane sulphonate (U50488) (0.01-1 microM) produced a concentration-dependent depression of the excitatory post-synaptic potential evoked by electrical stimulation of afferent inputs to the locus coeruleus. This effect was antagonized by naloxone with an apparent dissociation equilibrium constant (Kd) of 28 nM. U50488 did not completely abolish the EPSP. Over the same concentration range U50488 had no effect on the resting membrane potential, input resistance or action potential waveform of locus coeruleus neurons, nor did U50488 depress the depolarization produced by local application of L-glutamic acid. The mu opioid receptor agonists [D-Ala2, NMe Phe4, Gly-ol5] enkephalin (0.003-1 microM) and [D-Ala2, NMe Phe4, Met(O)5] enkephalinol (0.003-1 microM) caused a membrane hyperpolarization concomitant with a fall in neuronal input resistance. These effects were concentration-dependent and antagonized by naloxone with an apparent Kd of 1.5 nM. Mu agonists also caused a depression of the tetrodotoxin resistant action potential. An in vitro autoradiographic study of [3H]bremazocine binding within the locus coeruleus revealed that, although the majority of binding appears to be to mu sites, a significant proportion was displaceable by unlabelled U50488 and thus represented kappa binding sites. The possibility that kappa opioid receptors may be located pre-synaptically within the locus coeruleus, and that activation of these receptors depresses excitatory synaptic input, is discussed.
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PMID:Kappa opioid receptor activation depresses excitatory synaptic input to rat locus coeruleus neurons in vitro. 303 41

Various reports have indicated that infection of polymorphonuclear leukocytes (PMNL) with influenza virus causes depression of their metabolic and chemotactic responses, but the effect the PMNL has on the life cycle of influenza virus has not been well defined. The studies reported here were undertaken to determine whether influenza virus could replicate within PMNL. Virus-infected and uninfected PMNL were labeled with [35S]methionine and analyzed by gel electrophoresis and fluorography for detection of newly synthesized proteins. Both host- and virus-specific proteins were produced within PMNL. By using indirect immunofluorescence techniques combined with flow cytometry, the expression of newly synthesized viral antigens was detected in virus-infected PMNL. Plaque assays on supernatant fluid from infected PMNL showed that infectious progeny were not produced, indicating that influenza virus infection of PMNL is abortive.
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PMID:Synthesis of viral proteins in polymorphonuclear leukocytes infected with influenza A virus. 304 49

Twenty-nine amino acids were analyzed in the sera of 105 adult Senegambian goitrous patients classified as stages I, II, and III according to World Health Organization recommendations. Mean serum concentration of all essential amino acids revealed highly significant drops (p less than 0.001) as goiter stage increased, except for methionine (Met). Most nonessential amino acids (NEAA) and intermediary metabolites were similarly characterized by a general decrease to the subnormal range, although some resisted depression in stages II and III. Homocystine (Hcy) demonstrated a unique pattern in that it was the only NEAA distinguished by regularly rising serum levels. These data are consistent with the view that endemic goiter is associated with overall stepwise downregulation in protein metabolism. In addition to iodine restriction, generalized malnutrition may aggravate the goitrogenic processes. Serum levels of Met and Hcy strongly suggest that the first step of the transsulfuration pathway is impaired in protein-depleted states due to cystathionine beta-synthase (EC 4.2.1.22) deficiency.
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PMID:Nutritional significance of alterations in serum amino acid patterns in goitrous patients. 308 Aug 69

Rats were trained to eat a 6% casein basal diet during a 3-hour period per day. They were then fed either the same 6% casein diet or a 44% casein diet for 3 hours. No food intake depression was observed in the rats eating 44% casein diet during the 3-hour period. Plasma ammonia and amino acids and brain amino acids were measured at 0, 4, 12 and 24 hours after presentation of the 6% or 44% casein diets. Plasma ammonia rose to 134 (p less than 0.01) and 110 micromolar (p less than 0.05) in the 44% casein fed rats at 4 and 12 hours, respectively, as compared to 67 and 53 micromolar, respectively, for the 6% casein fed rats. All plasma amino acid concentrations except methionine and glutamate were elevated (p less than 0.05) at 4 hours. In the brain, threonine, glutamine and tyrosine concentrations were elevated (p less than 0.05) at 4 hours after diet presentation. At 24 hours, valine, isoleucine, leucine, phenylalanine, and methionine concentrations were also elevated (p less than 0.05). Because intake of the 44% casein diet decreases the second day of its presentation, as noted in an earlier experiment, the increases in plasma ammonia and its possible entry into the brain as reflected by increased brain glutamine together with changes in amino acid concentrations should be considered collectively among possible metabolic signals affecting intake of high protein diets.
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PMID:Increase in plasma ammonia and amino acids when rats are fed a 44% casein diet. 320 Sep 19

The metabolite S-adenosyl-L-methionine (SAMe), when prepared as the stable p-toluene-sulfonate complex of its sulfate salt and given parenterally in high doses, appears to have mood-elevating effects in depressed adults. The material is remarkably well tolerated when given by injection or intravenous infusion for this purpose, even in elderly or demented patients. Assuming that the toluene sulfonate component is inert, SAMe appears to have central neuropharmacologic effects after systemic injection in high doses. Nevertheless, the functional consequences of these remain unclear and, indeed, the ability of exogenous SAMe to reach the brain, and especially neuronal cytoplasm, is limited. SAMe has small effects on monoamine metabolism and, after injection, appears to have effects on the microviscosity of cell membranes that may be related to stimulation of phospholipid synthesis. The recent introduction of an orally administered form of SAMe for use in the treatment of osteoarthritis promises to stimulate further study of SAMe in disease-associated depression, major depressive disorder, and other neuropsychiatric conditions.
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PMID:Neuropharmacology of S-adenosyl-L-methionine. 331 48


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