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)

[Phe1psi(CH2-NH)Gly2]-nociceptin-(1-13)NH2 is an nociceptin analogue which has been shown to be a selective antagonist of the nociceptin receptor in peripheral tissues. We now report that intrathecal [Phe1psi(CH2-NH)Gly2]-nociceptin-(1-13)NH2 produced a dose-dependent depression of the nociceptive flexor reflex in rats, an effect that is similar to nociceptin. The duration of depression produced by [Phe1psi(CH2-NH)Gly2]-nociceptin-(1-13)NH2 was significantly more prolonged than by nociceptin. The reflex depressive effect of nociceptin was not blocked by [Phe1psi(CH2-NH)Gly2]-nociceptin-(1-13)NH2. The results indicated that the proposed nociceptin receptor antagonist [Phe1psi(CH2-NH)Gly2]-nociceptin-(1-13)NH2 is a potent agonist in rat spinal cord and more resistant to enzymatic degradation compared to nociceptin.
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PMID:[Phe1psi(CH2-NH)Gly2]-nociceptin-(1-13)NH2, a proposed antagonist of the nociceptin receptor, is a potent and stable agonist in the rat spinal cord. 968 33

Carcinus maenas and Necora puber were exposed to air for 72 h and 18 h, respectively, at 18 degreesC. Nitrogen excretion, blood and muscle ammonia content and blood urate and lactate content were recorded throughout the experimental emersion and following reimmersion (recovery period). During emersion, the rate of ammonia excretion was strongly reduced in both species, while urea and amine excretion were not enhanced. Blood and muscle ammonia content increased steadily, reaching 1.3 and 10.4 mmol l-1, respectively, after an 18 h emersion in N. puber. In contrast, in C. maenas, blood ammonia levels increased slightly during the first 12 h and then remained at this level (approximately 0.12 mmol l-1) until the end of emersion. Muscle ammonia content showed a non-significant increase at 12 h, after which values returned to control values (3.3 mmol l-1) for the next 60 h. Blood urate and lactate content increased in emersed N. puber, indicating strong internal hypoxia, but urate content did not increase in C. maenas until the third day of emersion. Upon reimmersion, both species released large amounts of ammonia within a few minutes. Two different patterns of ammonia release then were observed: ammonia excretion was enhanced for a further 3 h in N. puber, whereas raised ammonia excretion rates were observed for a further 24 h in C. maenas. These patterns, the recovery of blood and muscle ammonia levels and the calculated nitrogen balance between emersed and control crabs indicated that specific processes were used to manage the nitrogen overload induced by air exposure. Whereas N. puber shows little or no ability to limit ammonia accumulation in its body, C. maenas exhibits strong regulation of its nitrogen metabolism. The probability that amino acid synthesis is involved in this regulation and whether these species use metabolic depression as a survival strategy are discussed.
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PMID:Nitrogen metabolism of two portunid crabs, carcinus maenas and necora puber, during prolonged air exposure and subsequent recovery: a comparative study 969 86

A 4 x 4 Latin square experiment was conducted to examine abomasal passage of biogenic amines in steers fed silage and their related effects on intake, digestibility, and digestive function. Thirty percent of the dry matter (DM) in the diets consisted of alfalfa forage, which was fed as either hay or silage. The DM from alfalfa silage DM was substituted at 0, 33, 67, and 100% for DM from alfalfa hay and was fed to four ruminally and abomasally cannulated steers. The roughage component of the diet constituted 50% of the DM and consisted of 60% alfalfa silage or hay and 40% tropical corn silage. The concentrate was composed mainly of ground corn. The concentrations of putrescine and cadaverine in abomasal digesta increased as alfalfa silage in the diet increased. Abomasal recovery of biogenic amines, a product of their concentration in abomasal digesta and the passage of DM through the abomasum, was negatively correlated with intake. Abomasal recovery of most amines was 5 to 20% of intake. Abomasal recovery of cadaverine was correlated with depressed intake. Total DM intake was reduced 8.3 to 25.8% as the proportion of alfalfa silage in the diet increased. Frequency of reticular contractions, intake, ruminal DM digestibility, ruminal outflow, volatile fatty acids, and total tract DM digestibility decreased in steers fed diets that contained more alfalfa silage. Ruminal fluid pH and NH3 concentration increased in steers fed more alfalfa silage; however, mass and the DM percentage of ruminal contents decreased linearly. Postprandial insulin concentrations were quadratically related to the proportion of alfalfa hay or silage in the diet. Intraruminal metabolism of biogenic amines is extensive based on the relatively low quantities recovered in abomasal digesta; however, the amounts recovered in abomasal digesta were related to intake depression and associated physiological effects.
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PMID:Biogenic amines in silage, apparent postruminal passage, and the relationship between biogenic amines and digestive function and intake by steers. 974 85

Evidence suggests both opioid mu and delta receptors may participate in the regulation of respiration at different central nervous system sites. In the past, the overlapping receptor specificity of various opioid drugs has made it difficult to dissect the receptor subtype-specific activities involved in respiratory regulation. The new family of delta receptor selective agents such as cyclic[D-Pen2, 5]enkephalin, deltorphins, (+)-4-((alpha-R)-alpha-((2S,5R)-4-allyl-2, 5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide, naltrindole and H-Tyr-Tic(psi)[CH2NH]Phe-Phe-OH have now made it feasible to more clearly define the role of delta receptors in respiratory control. In a series of experiments we observed that systemic infusion of rats with the highly mu receptor-specific opioid alfentanil induced antinociception and hypercapnia, and both of these effects were antagonized by the mu antagonist D-Phe-Cys-Tyr-Orn-Thr-Pen-Thr-NH2. However, peripheral administration of the delta receptor antagonist naltrindole reverses the hypercapnia but not the antinociceptive activity of alfentanil. This differential effect of naltrindole on antinociception and hypercapnia could also be produced with the delta agonist (+)-4-((alpha-R)-alpha-((2S,5R)-4-allyl-2, 5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide. In addition, intracerebroventricular delivery of a number of peptide delta ligands cyclic[D-Pen2,5]enkephalin, deltorpnin II and H-Tyr-Tic(psi)[CH2NH]Phe-Phe-OH also produced the same differential reversal of hypercapnia without affecting antinociception. Thus, both the traditional delta agonists and antagonists are able to reverse the alfentanil-induced hypercapnia without affecting antinociception. The reversal of alfentanil-induced hypercapnia by these delta ligands was antagonized by a novel synthetic delta antagonist cis-4-(alpha-(4-((Z)-2-butenyl)-3, 5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide. We propose that in this experimental respiration model, the delta antagonists naltrindole and H-Tyr-Tic(psi)[CH2NH]Phe-Phe-OH behave like delta agonists with low but sufficient intrinsic activities to reverse alfentanil-induced hypercapnia in rats. The results suggest that a function of the delta receptor is to modulate or counteract the respiratory depression induced by the mu receptor.
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PMID:Delta-opioid ligands reverse alfentanil-induced respiratory depression but not antinociception. 986 59

The novel opioid tetrapeptides, endomorphin-1 and endomorphin-2, recently isolated from bovine and human brain bind with high affinity and selectivity to central mu-opioid receptors. In the digestive tract, a comprehensive pharmacological analysis of the receptors involved in endomorphin action has not been reported. In this study, we analyzed the effects of endomorphin-1 and endomorphin-2 on longitudinal muscle-myenteric plexus preparations (LMMPs) from the guinea-pig ileum. Both peptides (30 pM - 1 microM) inhibited (-log EC50 values: 8.61 and 8.59, respectively) the amplitude of electrically-induced twitch contractions in a concentration-dependent fashion, up to its abolition. Conversely, in unstimulated LMMPs, they failed to affect contractions to applied acetylcholine (100 nM). In stimulated LMMPs, the highly selective mu-opioid receptor antagonist, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), caused a concentration-dependent (30 nM-1 microM), parallel rightward shift of endomorphin-1 and endomorphin-2 inhibitory curves, without depression of their maximum. Following Schild analysis, calculated pA2 values were 7.81 and 7.85, respectively, with slopes not different from unity. Concentration-response curves to both peptides were not affected by 30 nM naltrindole (a selective delta-receptor antagonist) or 30 nM nor-binaltorphimine (a selective kappa-receptor antagonist). These results demonstrate that endomorphins selectively activate mu-opioid receptors located on excitatory myenteric plexus neurons, and that they act as full agonists.
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PMID:Endomorphin-1 and endomorphin-2 activate mu-opioid receptors in myenteric neurons of the guinea-pig small intestine. 987 30

The recently available antagonist selective for novel nociceptin receptor, [Phe1 psi(CH2-NH)Gly2]NC(1-13)NH2, was utilized in this study to verify specificity of nociceptin receptor in mediating the nociceptin-induced inhibition of electrical activity of neurons in the rostral ventrolateral medulla of rat brain slices. Perfusion of nociceptin (10 nM) considerably reduced spontaneously firing frequency of the medullary neurons. Co-perfusion of [Phe1 psi(CH2-NH)Gly2]NC(1-13)NH2 (10 microM) completely blocked the nociceptin-induced depression of the neuronal activity. Blocking effect of [Phe1 psi(CH2-NH)Gly2]NC(1-13)NH2 was concentration-dependent. However, the nociceptin antagonist did not modify basal, and opioid peptide enkephalin-depressed, firing rates of the neurons. In contrast to [Phe1 psi(CH2-NH)Gly2]NC(1-13)NH2, the non-selective opioid receptor antagonist naloxone (10 microM) failed to affect the nociceptin inhibition even though naloxone at a lower concentration (1 microM) readily blocked enkephalin-induced depression of the neuronal activity. These data indicate that the nociceptin-induced inhibition of spontaneous discharge of the rostral ventrolateral medulla neurons is specifically mediated by [Phe1 psi(CH2-NH)Gly2]NC(1-13)NH2-sensitive nociceptin receptors distinct from typical naloxone-sensitive opioid receptors.
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PMID:The nociceptin receptor-mediated inhibition of the rat rostral ventrolateral medulla neurons in vitro. 992 Jan 84

The reciprocal interactions between galanin and 5-HT1A receptors in the rat brain are presented. Galanin and its NH2-terminal fragments antagonize 5-HT1A receptor-mediated transmission at the postjunctional level, whereas galanin receptor activation mimics the inhibitory action of 5-HT1A receptor activation at the soma-dendritic level, leading to reductions of 5-HT metabolism and release. These interactions have been shown in both receptor binding studies and functional studies. In view of the present findings, galanin antagonists may represent a new type of anti-depressant drug, based on the 5-HT hypothesis of depression, by enhancing 5-HT release and postjunctional 5-HT1A-mediated transmission. Moreover, following intracerebroventricular injection galanin was found to be internalized in a population of hippocampal nerve cells mainly representing GABA, somatostatin, and/or NPY-immunoreactive nerve cells. The relevance of these findings is discussed in relation to the concept of volume transmission.
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PMID:Galanin modulates 5-hydroxytryptamine functions. Focus on galanin and galanin fragment/5-hydroxytryptamine1A receptor interactions in the brain. 992 78

1. Using whole-cell patch clamp recording from neurones in an in vitro slice preparation, we have examined opioid- and orphanin FQ (OFQ)-mediated modulation of synaptic transmission in the rat arcuate nucleus and ventromedial hypothalamus (VMH). 2. Application of OFQ activated a Ba2+-sensitive and inwardly rectifying K+ conductance in approximately 50 % of arcuate nucleus neurones and approximately 95 % of VMH neurones. The OFQ-activated current was blocked by the nociceptin antagonist [Phe1Psi(CH2NH)Gly2]-nociceptin(1-13) NH2 (NCA), a peptide that on its own exhibited only weak agonist activity at high concentrations (> 1 microM). Similar current activation was observed with the mu agonist DAMGO but not delta (DPDPE) or kappa (U69593) agonists. 3. In arcuate nucleus neurones, DAMGO (1 microM), U69593 (1 microM) and OFQ (100 nM to 1 microM) but not DPDPE (1 microM) were found to depress the amplitude of electrically evoked glutamatergic postsynaptic currents (EPSCs) and decrease the magnitude of paired-pulse depression, indicating that opioid receptors were located presynaptically. 4. In VMH neurones, DAMGO strongly depressed the EPSC amplitude in all cells examined. DAMGO decreased the magnitude of paired-pulse depression, indicating that mu receptors were located presynaptically. U69593 weakly depressed the EPSC while OFQ and DPDPE had no effect. 5. In VMH neurones, DAMGO depressed the frequency of miniature EPSCs (-58 %) in the presence of tetrodotoxin and Cd2+ (100 microM), suggesting that the actions of mu receptors could be mediated by an inhibition of the synaptic vesicle release process downstream of Ca2+ entry. 6. The data presented show that presynaptic modulation of excitatory neurotransmission in the arcuate nucleus occurs through mu, kappa and the orphan opioid ORL-1 receptors while in the VMH presynaptic modulation only occurs through mu opioid receptors. Additionally, postsynaptic mu and ORL-1 receptors in both the arcuate nucleus and VMH modulate neuronal excitability through activation of a K+ conductance.
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PMID:Pre- and postsynaptic actions of opioid and orphan opioid agonists in the rat arcuate nucleus and ventromedial hypothalamus in vitro. 1033 93

Antifreeze polypeptides from fish are generally thought to inhibit ice crystal growth by specific adsorption onto ice surfaces and preventing addition of water molecules to the ice lattice. Recent studies have suggested that this adsorption results from hydrogen bonding through the side chains of polar amino acids as well as hydrophobic interactions between the non-polar domains on the ice-binding side of antifreeze polypeptides and the clathrate-like surfaces of ice. In order to better understand the activity of one of the antifreeze polypeptide families, namely the alpha-helical type I antifreeze polypeptides, four alpha-helical peptides having sequences not directly analogous to those of known antifreeze polypeptides and containing only positively charged and non-polar side chains were synthesized. Two peptides with regularly spaced lysine residues, GAAKAAKAAAAAAAKAAKAAAAAAAKAAKAAGGY-NH2 and GAALKAAKAAAAAALKAAKAAAAAALKAAKAAGGY-NH2, showed antifreeze activity, albeit weaker than seen in natural antifreeze polypeptides, by the criteria of freezing point depression (thermal hysteresis) and ice crystal modification to a hexagonal trapezohedron. Peptides with irregular spacing of Lys residues were completely inactive. Up to now, lysine residues have not been generally associated with antifreeze activity, though they have been implicated in some antifreeze polypeptides. This work also shows that lysine residues in themselves, when properly positioned on an alpha-helical polyalanine scaffold, have all the requisite properties needed for such an activity.
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PMID:Artificial antifreeze polypeptides: alpha-helical peptides with KAAK motifs have antifreeze and ice crystal morphology modifying properties. 1043 7

After its discovery in 1931, substance P (SP) remained the only mammalian member of the family of tachykinin peptides for several decades. Tachykinins thus refer to peptides sharing the common C-terminal amino acid sequence Phe-X-Gly-Leu-Met x NH2. In recent years the family of mammalian tachykinins has grown with the isolation of two novel peptides from bovine and porcine central nervous system (CNS), neurokinin A and neurokinin B. In parallel with the identification of multiple endogenous tachykinins several classes of tachykinin receptors were discovered. The receptors described so far are named tachykinin NK1 receptor, tachykinin NK2 receptor and tachykinin NK1 receptor, respectively. The present review focuses on the pharmacology and putative function of tachykinin NK1 receptors in brain. The natural ligand with the highest affinity for the tachykinin NK1 receptor is SP itself. The C-terminal sequence is essential for activity, the minimum length of a fragment with reasonable affinity for the tachykinin NK1 receptor is the C-terminal hexapeptide. A rapid advance of knowledge was caused by development of non-peptidic tachykinin NK1 receptor antagonists. This area is under rapid development and a variety of different chemical classes of compounds are involved. Species-dependent affinities of tachykinin NK1 receptor antagonists reveal two clusters of compounds, targeting the tachykinin NK1 receptor subtype found in guinea pig, human or ferret or the one in rat or mouse, respectively. The most recently developed compounds are highly selective, enter the brain and are orally bioavailable. Distinct behavioural effects in experimental animals suggest the involvement of tachykinin NK1 receptors in nociceptive transmission, basal ganglia function or anxiety and depression. Recent clinical trials in man showed that tachykinin NK1 receptor antagonists are effective in treating depression and chemotherapy-induced emesis. Therefore, it is well possible that tachykinin NK1 receptor antagonists will be clinically used for treatment of specific CNS disorders within a short period of time.
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PMID:The tachykinin NK1 receptor in the brain: pharmacology and putative functions. 1044 64


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