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 intracerebroventricular (i.c.v.) or systemic injections of Met- or Leu-enkephalin, beta-endorphin, FK 33.824 (D-Ala2, MePhe4, Met(O5)-ol-enkephalin) and of morphine and naloxone have been studied in baboons, Papio papio, which spontaneously show photically induced epileptic responses. Animals were chronically implanted with epidural or deep recording electrodes and a cannula in one lateral ventricle, and tested whilst seated in a primate chair. In some animals the natural syndrome was enhanced by the prior administration of DL-allylglycine, 100--200 mg/kg, i.v. Met- or Leu-enkephalin, 1--10 mg, i.c.v., did not lead to any manifest focal or generalized seizure discharges. Nor did it lead to any consistent enhancement or reduction of photically induced myoclonic responses (as tested 5--10 min after injection). beta-Endorphin, 0.1--0.5 mg, i.c.v., did not enhance or impair photically induced myoclonic responses. FK 33.824, 0.1--0.5 mg, i.c.v., depressed respiration and slowed EEG background rhythms for 9--15 h. This was associated with a loss of myoclonic responses to photic stimulation. These effects were reversed for 20--40 min following the injection of naloxone, 1 mg/kg i.m. A depression of respiration and a slowing of EEG rhythms was seen beginning 5--20 min after FK 33.824, 2 or 4 mg/kg, i.v. The higher dose also abolished photically induced myoclonic responses. Naloxone, 1 mg/kg, definitively reversed these effects. Morphine, 5--10 mg i.c.v., tended to increase the latency to onset of generalized myoclonus during photic stimulation. Myoclonic responses were delayed or diminished after morphine, 5 mg/kg, i.m. Naloxone, 1--2 mg/kg i.m., reversed this effect. Naloxone, 0.2--5.0 mg/kg i.m., alone, did not significantly modify photically induced myoclonus, either in animals of low or high initial responsiveness, or in those pretreated with allylglycine.
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PMID:Effects of opiate-like peptides, morphine, and naloxone in the photosensitive baboon, Papio papio. 22 24

The relationship between neutrophil polymorphonuclear leukocyte (PMN) locomotion and the exocytosis of neutrophil cytoplasmic granules was studied by assessing these processes in cells migrating through micropore filters and by measuring the effects of degranulating stimuli on PMN chemotaxis, orientation, adhesiveness, and ability to bind the chemoattractant f-Met-Leu-[3H]Phe. Studies of cells migrating through cellulose nitrate filters indicated that concentrations of f-Met-Leu-Phe optimal for exocytosis were greater than those optimal for chemotaxis and actually inhibited cell migration. In other studies incubation of PMNs with concentrations of secretagogues causing exocytosis of 30% or greater PMN lysozyme increased cell adhesiveness and inhibited chemotaxis. PMNs that had secreted more than 30% lysozyme appeared round, did not orient in a gradient of chemoattractant, and were capable of significantly less f-Met-Leu-[3H]Phe binding than were control cells. The decreased binding of f-Met-Leu-Phe was not associated with hydrolysis of chemotactic peptide by washed cells, although peptide hydrolysis was caused by cell products secreted extracellularly after vigorous exocytosis. In contrast, when only 10--15% cellular lysozyme was released f-Met-Leu-Phe binding was enhanced significantly and there was no depression of chemotaxis. The data indicate limited exocytosis of intracellular granule contents is associated with increased availability of PMN cehmotactic factor receptors. Vigorous exocytosis is associated with inactivation of chemotactic responsiveness related to increase cell adhesiveness, decreased PMN binding of chemotactic factors, and to hydrolysis of chemoattractants by factors secreted extracellularly.
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PMID:Role of secretory events in modulating human neutrophil chemotaxis. 37 35

The importance of adhesion in regulating locomotion and accumulation of polymorphonuclear leukocytes (PMN) has remained vague. We found that the chemotaxis of human PMN resuspended in heat-inactivated plasma was maximal toward 1-10 nM N-formyl-met-leu-phe (f-Met-Leu-Phe), but fell below random motility toward >/= 100 nM. This impressive decrease of motility was paralleled by increased cell adherence on Petri dishes being minimal at 1 nM and maximal at >10 nM f-Met-Leu-Phe (6+/-1 and 37+/-2% [SE] adherent cells, respectively). Checked by phase-contrast microscopy, cells under stimulated adhesion lost the typical bipolar shape of moving PMN and became immobilized and highly flattened. PMN, preexposed to 250 nM f-Met-Leu-Phe and tested after washing, retained increased adhesiveness and showed extremely low random and chemotactic motility. In contrast, preexposure to 1 nM f-Met-Leu-Phe had no effect on chemotaxis. Supporting the concept that immobilizing hyperadhesiveness does not correspond to a general functional hyporesponsiveness of PMN, no depression of the initial ingestion rate was observed in the presence of 250 nM f-Met-Leu-Phe. Moreover, a close correlation was found between the induction of PMN adhesiveness and the stimulation of the hexose monophosphate pathway activity as well as of lysomal enzyme release (r >/= 0.98). Thus, "chemotactic deactivation" and "high-dose inhibition of chemotaxis" by N-formyl peptides is the consequence of increased cell adhesiveness. This phenomenon provides a mechanism for cell trapping at the inflammatory site. Conversely, if operative in circulating blood, e.g., in septicemia, it may impair PMN emigration to such sites.
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PMID:Modulating influence of chemotactic factor-induced cell adhesiveness on granulocyte function. 44 62

1. The synthetic Met-enkephalin, D-Ala-2-Me-Phe-4-Met-(O)-ol-enkephalin (FK 33-824). 1 or 2 micrograms, after its injection into the nucleus tractus solitarius (NTS) of Wistar rats, anesthetized with pentobarbital and breathing spontaneously, produced a transient increase in blood pressure followed by sustained and significant (P less than 0.05) hypotension and bradycardia. This occurred in a dose dependent manner. 2. FK 33-824 in the NTS, 1 or 2 micrograms, also produced a marked respiratory depression. 3. In anesthetized rats, in which hypoventilation was prevented by mechanical ventilation, there was a definite reduction in blood pressure and heart rate that was considerably and significantly (P less than 0.05) less than that observed in spontaneously breathing rats. 4. Blood pressure fluctuations occurred after NTS injection that were more marked in spontaneously breathing animals but still occurred in animals that were ventilated mechanically. 5. FK 33-824, 1 and 2 micrograms in the NTS was fatal within 100 min for all animals but was prevented by mechanical ventilation. Higher doses of FK 33-824, 10 micrograms in the NTS, however, induced fatal ventricular arrhythmias even in the mechanically ventilated rat. 6. Thus, FK 33-824 in the NTS decreases blood pressure and heat rate in spontaneously breathing as well as mechanically ventilated rats, but much of the effect on blood pressure and heart rate is due to the profound respiratory depression in the spontaneously breathing rat.
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PMID:D-Ala-2-Me-Phe-4-Met-(O)-ol-enkephalin in the nucleus tractus solitarius of the rat produces cardiorespiratory depression. 186 20

The purpose of this study was to investigate the effect of the synthetic Met-enkephalin, D-Ala-2-Me-Phe-4-Met-(O)-ol-enkephalin (FK 33-824), on blood pressure, heart rate, respiratory rate and survival, after its injection into the 4th cerebral ventricle of Wistar rats. The animals were either anesthetized with pentobarbital and breathing spontaneously or unanesthetized. The unanesthetized rats were previously instrumented with cannulas in the 4th cerebral ventrical and a systemic artery. In anesthetized rats, intracerebroventricular administration of FK 33-824 produced a transient increase in blood pressure followed by sustained hypotension, bradycardia and respiratory depression in a dose-dependent manner. Fatalities were observed over a 150-min observation period and were a function of dose. Pretreatment with atropine sulfate (1 mg/kg i.v.) produced an accentuated response with greater hypotension, bradycardia and shorter survival. In another group of anesthetized rats, in which hypoventilation was prevented by mechanical ventilation, blood pressure and heart rate were not as reduced as in spontaneously breathing rats. Hypotension, bradycardia and hypoventilation were less marked in unanesthetized rats, compared to anesthetized rats. Thus, FK 33-824 in the 4th cerebral ventricle of the rat produces marked changes in blood pressure in anesthetized as well as unanesthetized animals, but these changes were less in the unanesthetized or mechanically ventilated animal and greater after atropine, suggesting that these effects are mediated by respiratory depression and are antagonized by the cholinergic nervous system.
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PMID:Cardiorespiratory responses to D-Ala-2-Me-Phe-4-Met-(O)-ol-enkephalin after administration into the fourth cerebral ventricle of the rat: interaction with cholinergic mechanisms. 206 74

The toxicity of Cu, Ni and Fe individually, as well as in combination (Cu + Ni, Cu + Fe, Ni + Fe), on growth-rate depression, uptake of NO3- and NH4+, photosynthesis, nitrate reductase and urease activity of Chlorella vulgaris has been studied. All the test metals when used individually showed pronounced toxicity on all the parameters studied. However, their interactive effect was mostly antagonistic except for Cu + Ni (synergism). Pre-addition of Fe offered more protection to the cells against copper and nickel toxicity. The data of statistical analysis reconfirmed that 14CO2 uptake is the most sensitive parameter (significant at P less than 0.005, both for time and treatment) than others in metal toxicity assessment. However, these results suggest further that exposure time and sequence of metal addition are very important in biomonitoring of heavy metal toxicity.
Biol Met 1990
PMID:Impact of bimetallic combinations of Cu, Ni and Fe on growth rate, uptake of nitrate and ammonium, 14CO2 fixation, nitrate reductase and urease activity of Chlorella vulgaris. 216 14

1. Actions of the neuropeptide FMRFamide (Phe-Met-Arg-Phe-NH2) and its derivative YGG-FMRFamide (Tyr-Gly-Gly-Phe-Met-Arg-Phe-NH2) on Ca2+ current were examined in identified, voltage-clamped neurones in the abdominal ganglion of Aplysia californica. 2. 'Puffed' application of either peptide at concentrations of 1-50 microM was followed by a transient partial suppression of pharmacologically isolated inward Ca2+ current elicited by a depolarizing step. At 20 degrees C, suppression was maximal 10-25 s following the brief puff of peptide, and lasted up to 90 s. Bath application of peptide had a steady suppressing effect, showing little if any desensitization. 3. Alternative sources of inward current suppression were ruled out, indicating that application of FMRFamide or YGG-FMRFamide produces a true decrease in Ca2+ current, rather than enhancement of possible contaminating outward (K+, H+ or Cl-) currents. 4. FMRFamide and YGG-FMRFamide were equally effective in suppressing Ca2+ current (apparent dissociation constant, KD* approximately 10 microM). However, only 30-50% of the total Ca2+ current elicited by voltage steps to above +10 mV appeared to be susceptible to suppression by even saturating concentrations of peptide. This, as well as a reduced effect of the peptides on Ca2+ current which was observed at potentials below +10 mV, may perhaps result from the presence of more than one class of Ca2+ channels, only one of which is sensitive to FMRFamide. 5. FMRFamide eliminated a constant fraction of Ca2+ current at all potentials above +10 mV, and had no direct effect on activation or inactivation of the remaining current. This behaviour is consistent with reduction in the number of functional Ca2+ channels by the peptide. 6. Suppression of Ca2+ current produced a concomitant depression of Ca2+-dependent K+ current, which was shown previously to be insensitive to FMRFamide when activated by direct ionophoretic injection of Ca2+ into the cell. 7. The effect of FMRFamide on Ca2+ current was normal following interference with or activation of known second-messenger systems, those involving adenosine 3',5'-cyclic monophosphate (cyclic AMP), cyclic GMP, Ca2+, inositol trisphosphate and protein kinase C. 8. Suppression of Ca2+ current by FMRFamide appeared to be mediated by the same receptor as enhancement by the peptide of K+ current resembling IK(S) (K+ current suppressed by serotonin), an effect seen in most of the same cells. Both effects of FMRFamide were mimicked by injection of guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) into the cell, suggesting that the peptide may exert its effects by activating a guanosine 5'-triphosphate (GTP)-binding protein
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PMID:Suppression of calcium current by an endogenous neuropeptide in neurones of Aplysia californica. 244 95

The endogenous opioids and their receptors are known to play a major role in neoplasia. In the present study, naltrexone (NTX), a potent opioid antagonist, was utilized to explore the interactions of opioids and opioid receptors in mice with transplanted neuroblastoma (S20Y). Tumors from mice subjected to either intermittent (4-6h/day; 0.1 mg/kg NTX) or complete (24 h/day; 10 mg/kg NTX) opioid receptor blockade exhibited an up-regulation of DADLE and Met-enkephalin binding sites, as well as tissue levels of beta-endorphin and Met-enkephalin. Binding affinity to [D-Ala2,D-Leu5]enkephalin (DADLE) or ethylketocyclazocine (EKC), the levels of plasma beta-endorphin, and the anatomical location and quantity of Met- and Leu-enkephalin and cytoskeletal components (i.e. tubulin, actin, brain spectrin (240/235) were similar in NTX and control tumor-bearing animals. Tissue viability of the 0.1 NTX group was increased compared to controls. Both mitotic and labeling indexes were increased during the period of opioid receptor blockade, but decreased in the period subsequent to receptor blockade. NTX treatment produced a 2-fold increased in sensitivity to opioids. Met-enkephalin (10 mg/kg) produced a depression in both mitotic and labeling indexes in tumor-bearing mice that could be reversed by naloxone (10 mg/kg) administration. Thus, the endogenous opioids are trophic agents that inhibit growth by suppressing cell proliferation. The duration of receptor blockade by opioid antagonists modulates these actions, affecting both tumor incidence and survival time. Complete opioid receptor block prevents the interaction of increased levels of putative growth-related peptides with a greater number of opioid receptors, thereby increasing cell proliferation and accelerating tumor growth. With intermittent blockade, an enhanced opioid-receptor interaction occurs during the interval when the opioid antagonist is no longer present, producing an exaggerated inhibitory action on cell proliferation and the repression of tumorigenic events.
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PMID:Opioid antagonist modulation of murine neuroblastoma: a profile of cell proliferation and opioid peptides and receptors. 254 Aug 73

The purpose of this study was to investigate the cardiorespiratory effects of the synthetic Met-enkephalin, D-Ala-2-Me-Phe-4-Met-(0)-ol enkephalin (FK 33-824) after its administration into the anterior hypothalamic area, paraventricular hypothalamic nuclei and third ventricle. Wistar rats, anaesthetised with pentobarbitone and breathing spontaneously, received an injection of FK 33-824, 1 or 2 micrograms into one of these three areas. FK 33-824 produced significant (analysis of variance, p less than 0.05) and sustained hypotension of similar degree following injection into any one of these three sites. Significant (p less than 0.05) reductions in heart rate and respiratory rate were also observed. Hypotension and bradycardia occurred, but to a lesser degree, when respiratory depression was prevented by mechanical ventilation. FK 33-824 produced fatal bradyarrhythmias in spontaneously breathing and mechanically ventilated animals. When respiratory depression was prevented by mechanical ventilation, survival was lowest after third ventricular administration followed by paraventricular and anterior hypothalamic injections. Thus D-Ala-2-Me-Phe-4-Met-(0)-ol enkephalin produced marked vasodepression and respiratory depression in the rat. These effects were interrelated but reductions in heart rate and blood pressure also occurred independently of the respiratory depression.
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PMID:Cardiorespiratory effects of D-Ala-2-Me-Phe-4-Met-(0)-ol enkephalin in the third ventricle, and in anterior hypothalamic and paraventricular areas of the rat brain. 262 Mar 18

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


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