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

Fourteen di- and tripeptide analogues of MIF, Pro-Leu-Gly-NH2, have been synthesized and assayed for inhibition of oxotremorine-induced tremor. Replacement of Pro by HCO-Pro or cyclopentanecarboxylic acid gave inactive analogues, while some peptides of the general structure less than Glu-Leu-Gly-NR1R2 were highly active. Thus, R1 = C3H8 and R2 = H gave 4 times the activity of MIF, R1 = I-C3H8 and R2 = H gave 13 times the activity of MIF, and R1 = R2 = CH3 gave 29 times the activity of MIF. cyclo(-Pro-Leu-), Pro-Lys-Gly-NH2, and Pro-Arg-Gly-NH2 had no activity. Apparently, small modifications in the structure of MIF can yield highly active analogues with potential clinical value, e.g., in the treatment of Parkinson's disease or mental depression.
 ...
PMID:Tripeptide analogues of melanocyte-stimulating hormone release-inhibiting hormone (Pro-Leu-Gly-NH2) as inhibitors of oxotremorine-induced tremor. 4 28

Development of the effect of glycine and gamma-aminobutyric acid [GABA] on spontaneous motility was studied in 11- to 19-day-old chick embryos under normal conditions and after acute and chronic decapitation. Chronic decapitation was performed on the 2nd day of incubation. Glycine (100 mg/kg egg weight) and GABA (103 mg/kg egg weight) (applied onto the shell membrane) demonstrably inhibited spontaneous motility only from the 15th day of incubation, the inhibitory effect increasing with the embryo's age. When administered together in half doses, glycine and GABA completely inhibited spontaneous motility for the first time in 19-day-old embryos. Neither amino acid influenced depression of motility immediately after decapitation, but 24 and 48 hours after, in 17- and 19-day-old embryos, they had a paradoxical effect, i.e. they transiently activated motor activity and even caused motor paroxysms. After chronic decapitation, both glycine and GABA again had a mild, protracted inhibitory effect. A comparison of spontaneous motility in normal and chronically decapitated embryos showed that the role of supraspinal factors in spinal motor output increases significantly with development of the chick embryo from the 15th day of incubation and that inhibition of these supraspinal factors plays the decisive role in the effect of glycine and GABA.
 ...
PMID:Development of spontaneous motility in chick embryos. The spinal and supraspinal component of the inhibitory effect of glycine and GABA. 14 12

Incubation of the CFs Gly-His-Glyc or CCF with PMNs in the absence of a gradient, resulted in a dose-dependent depression in chemotactic activity when, after washing, the cells were challenged with the CFs in a Boyden chamber. When the cells were preincubated with either CF and suitable concentrations of colchicine, the inhibition of chemotaxis that either of these agents induced when incubated with the cells alone was abolished. Deactivation reappeared when the optimal ratio between colchicine and CF was altered in either direction. Ultramicroscopic studies showed an increase in centriole-associated microtubules following incubation of cells with CFs. This increase was arrested by prior exposure of the cells to colchicine. Colchicine did not alter the specific binding of CCF to human neutrophils, and lumicolchicine had no effect on either chemotaxis or deactivation. Our data suggest that the control of PMN chemotaxis is predicted upon microtubule assembly evoked by cell interaction with a chemotactic gradient. Chemotaxis would be prevented by conditions that inappropriately organize responsive microtubules in either a polymerized or depolymerized configuration.
 ...
PMID:A proposed model for chemotactic deactivation: evidence for microtubule modulation of polymorphonuclear leukocyte chemotaxis. 45 52

The addition of glutamate to the bathing medium increased the average firing rate of cerebellar rat Purkinje cells in vitro. At concentrations lower than 10(-6) M, there was no deviation from controls in the firing pattern or rate that was detectable. At 10(-3) M glutamate, the amplitude of the action potentials was gradually decreased until all activity was abolished. The action of glutamate was rapid in onset and reversible. Glycine produced sustained depression of firing at concentrations higher than 10(-3) M. This inhibition was strychnine-insensitive and considered nonspecific. Strychnine, on the other hand, exerted an excitatory influence on Purkinje cells when applied at low concentrations (10(-8) TO 10(-6) M). The firing became more irregular and complex discharges appeared. Higher concentrations of strychnine (greater than 10(-5) M) inhibited the spontaneous activity. The effect of strychnine was partly reversible. The data suggest that low concentrations of strychnine lower the threshold for inputs at excitatory as well as inhibitory synapses.
 ...
PMID:Spontaneous bioelectric activity of cultured Purkinje cells during exposure to glutamate, glycine, and strychnine. 94 38

Several assays with young chicks fed crystalline amino acid diets were conducted to investigate the effects of supplemental glycine, serine, threonine, arginine, or adenine on the growth depression resulting from consumption of excess methionine. Glycine was partially effective in alleviating the growth depression caused by excess methionine. The addition of threonine together with glycine improved performance still further. Efficiency of food utilization for weight gain was greater in birds fed the methionine-imbalanced diet supplemented with glycine and threonine than in those fed the control diet. Supplemental glycine, threonine, or adenine, but not arginine, was effective in ameliorating the hypoglycemia resulting from consumption of excess methionine. The rate of oxidation of a tracer dose of threonine was increased markedly by feeding 1.25% excess methionine. This was reflected in a 20% depression in threonine utilization for weight gain as measured by slope ratio. The data suggest that both threonine and glycine are antagonized by consumption of excess methionine.
 ...
PMID:Methionine toxicity in the chick: nutritional and metabolic implications. 115 32

Intracellular recordings were made from neurons in a rat locus coeruleus slice preparation in vitro. A postsynaptic potential was evoked by electrical stimulation of afferents to the neurons. CI-977 ([5R-(5a,7a,8b)]-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec -8-yl[-4-benzofuranacetamide monohydrochloride) caused a depression of the evoked postsynaptic potential on locus coeruleus neurons. This action was reversed on washout. Bremazocine had a similar action on less than 50% of locus coeruleus neurons. Concentrations of CI-977 which depressed the postsynaptic potential did not affect either passive membrane conductance or a voltage-sensitive potassium current resembling IA. The depression of the excitatory postsynaptic potential caused by CI-977 remained in the presence of either 30 microM bicuculline and picrotoxin or when potassium acetate-filled recording electrodes were used. Using potassium chloride-filled recording electrodes and in the presence of 30 microM 6-cyano-2,3-dihydro-7-nitroquinoxaline-2,3-dione and either 30 microM DL-2-amino-5-phosphonovaleric acid or 500 microM kynurenic acid, CI-977 had no effect on the postsynaptic potential. The effects of CI-977 were reversed by 30-100 nM naloxone and 1-10 nM norbinaltorphimine but not by 1-10 nM naloxone. The hyperpolarizing response to the mu-opioid receptor-selective agonist D-Ala2,Nme Phe4,Gly-ol5 (DAGOL) was blocked by 1-10 nM naloxone but not by 1-100 nM norbinaltorphimine. The hyperpolarizing response to DAGOL was not affected by high doses of CI-977.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:A highly selective kappa-opioid receptor agonist, CI-977, reduces excitatory synaptic potentials in the rat locus coeruleus in vitro. 131 40

The effects on C fiber evoked activity in lumbar dorsal horn convergent neurones of i.v. morphine alone, of Tyr-D-Thr-Gly-Phe-Leu-Thr (DTLET) alone or of either of these drugs in association with 5-deoxyadenosylcobalamine (dibencozide) were investigated in anesthetized rats. Both morphine and DTLET depressed the neuronal responses in a dose-related fashion, with the former requiring lower doses. Although dibencozide alone was devoid of any effect, it significantly enhanced the depressive effects of all doses of morphine tested and of the lower two doses of DTLET. It is concluded that dibencozide enhances the spinal depression of nociceptive information elicited by mu and delta opioid agonists. This drug could provide a useful tool for the study of interactions between opioids and opioids receptors. It is also suggested that dibencozide could be useful in clinical practice for reducing the dosage of opioids.
 ...
PMID:Depressive effects of mu and delta opioid receptor agonists on activities of dorsal horn neurones are enhanced by dibencozide. 164 26

A biochemical basis for the development of tolerance to morphine has yet to be defined. Although a number of models have been proposed, none can account for complete tolerance to this drug. Previous studies in our laboratory indicated that the development of complete tolerance to certain morphine-induced behaviors (antinociception, catalepsy and respiratory depression) is associated with changes in the activity of some form(s) of phosphodiesterase with cyclic GMP as substrate (cGMP-PDE) activity in the brain areas that mediate these behaviors (periaqueductal gray, striatum and medulla). In the present study, experiments were performed in which Cyclo(Leu-Gly), a dipeptide that inhibits the development of tolerance to morphine, was administered daily (2 mg/kg) to morphine-naive rats, coadministered with morphine or coadministered with morphine to morphine-tolerant rats and the cGMP-PDE activity was measured. The development of tolerance to the effects was inhibited or reversed by administration of cyclo(Leu-Gly) and there were corresponding changes in cGMP-PDE activity in various brain regions. Differences in cGMP hydrolysis between brain regions from morphine-tolerant animals, tolerance-inhibited animals and tolerance-reversed animals strengthens the evidence for direct involvement of cGMP-PDE(s) in tolerance phenomena.
 ...
PMID:Effect of cyclo(Leu-Gly) on cyclic GMP-phosphodiesterase activity changes associated with development of tolerance to morphine-induced antinociception, catalepsy, respiratory depression and mydriasis. 165 44

Effects of selective mu and delta receptor agonists on capsaicin-induced cough reflex in rats were studied. Intracisternal injection (i.cist.) of a selective mu receptor agonist [D-Ala2,Mephe4,Gly-ol5]enkephalin (DAMGO) produced dose-related depression of coughs over the 0.003-0.03 nmol dose range. The antitussive potency of DAMGO was 100-fold more potent than morphine. The antitussive effects of DAMGO and morphine were significantly reduced by naloxone (1 nmol i.cist.). The selective delta receptor agonist, [D-Pen2,D-Pen5]enkephalin (DPDPE), at a dose of 10 nmol (i.cist.), had no significant effect on the number of coughs. When co-administered i.cist., DPDPE (10 nmol) consistently and significantly decreased the antitussive potencies of DAMGO and morphine. The decrease in the antitussive effects of DAMGO and morphine caused by DPDPE were prevented by selective delta receptor antagonist, naltrindole (3 nmol). These results suggest that the antitussive effects of opioids are mediated predominantly by mu receptors, and delta receptors may play an inhibitory role in antitussive processes that are mediated by the mu receptors.
 ...
PMID:Modulation of mu-mediated antitussive activity in rats by a delta agonist. 166 89

The mechanism of disinhibition produced by opioid peptides was studied using intracellular recording in area CA1 of rat hippocampal slices. The mu-selective opioid peptide [D-Ala2,N-Me-Phe4,Gly-ol5]-enkephalin (DAGO) reversibly depressed directly-activated, monosynaptic inhibitory postsynaptic potentials (IPSPs) evoked in the presence of the excitatory amino acid receptor antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and D,L-2-amino-5-phosphonovalerate (APV) in a naloxone-sensitive manner. Depression of monosynaptic inhibitory postsynaptic potentials (IPSPs) by DAGO was not prevented by 1-2 mM Ba2+. DAGO reversibly depressed monosynaptic IPSPs when applied locally close to the recording site, but was ineffective when applied close to the stimulating site in stratum radiatum. These results suggest that DAGO disinhibits pyramidal neurons in area CA1 of the rat hippocampus by activating mu opiate receptors located on the terminals of inhibitory neurons, and by a Ba(2+)-insensitive mechanism.
 ...
PMID:Evidence for mu opiate receptors on inhibitory terminals in area CA1 of rat hippocampus. 167 56


1 2 3 4 5 6 7 8 9 10 Next >>