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)

The respiratory action of morphine, D-Ala2-D-Leu5-enkephalin, and D-Ala2-Me-Phe4-Met(O)ol5-enkephalin, restrictively applied to the dorso-rostral surface of the pons, was studied in anesthetized cats. Frequency was selectively and dose-dependently depressed, down to apnea, whereas tidal volume and its response to CO2 either remained unchanged or were increased. Similar effects were observed in vagotomized and decerebrate cats. From these and previous (1) results, it can be concluded that the medullary and pontine structures related to respiration are differentially affected by opioids. Pontine nuclei are more sensitive to opioid depression and account for changes in frequency, whereas medullary depression results in reduction of tidal volume and CO2 sensitivity.
 ...
PMID:Participation of pontine structures in the respiratory action of opioids. 636 54

A comparison was made in awake rats between the analgesic and the respiratory depressant actions induced by the mu-opiate agonists morphine and Tyr-D-Ala-Gly-N-Me-Phe-Met-(O)-ol (FK-33824), and the delta-agonists Tyr-D-Ala-Gly-Phe-D-Leu ( DADLE ) and Tyr-D-Ser-Gly-Phe-D-Leu-Thr (D-Ser2- Thr6 ), injected into the cerebral ventricles. The four opioids caused a dose-dependent analgesia (tail-flick); FK-33824 was the most potent, followed by morphine, DADLE and D-Ser2- Thr6 , and the duration of the analgesic effect of D-Ser2- Thr6 was very short. Respiratory frequency was dose-dependently depressed by FK-33824 and DADLE ; dose-response curves with morphine and D-Ser2- Thr6 could not be obtained for technical reasons. The in vivo apparent pA2 values for naloxone against the mu-agonist FK-33824 and the delta-agonist DADLE were similar in analgesia suggesting an interaction with the same type of receptor. On the other hand, in respiration studies the pA2 value for the interaction of naloxone with DADLE was significantly higher than with FK-33824. The ratio between the ED50 required to induce respiratory depression and analgesia was 1,500 times higher for FK-33824 than for DADLE . It was concluded that agonist interaction with mu-receptors can result in antinociceptive effect in the tail-flick test, whereas respiratory depression seems to require a prominent, but non-exclusive, interaction with delta-receptors.
 ...
PMID:A comparative study in rats of the respiratory depression and analgesia induced by mu- and delta-opioid agonists. 637 10

The use of naloxone (NAL), an opioid receptor antagonist, has provided indirect evidence that endogenous opioids contribute to cardiovascular depression during shock. To determine if endogenous opioids act centrally to influence cardiovascular function, injections of D-Ala2-Met-enkephalinamide (DAME), a potent Met-enkephalin analog, were made into the 3rd cerebral ventricle (ICV) of 5 conscious cynomulgus monkeys restrained in primate chairs. Systolic blood pressure (SBP) and heart rate (HR) were determined every 10 min during a 30-60 min control period and for up to 5 hr post-injection. Colonic temperature (Tc) was monitored continuously. SBP declined from baseline values with 50 and 100 micrograms (85.2 and 170.4 nM) doses but was significant (p less than 0.001) for only the 100 micrograms dose between 15-125 min post-injection. HR also decreased but did not exhibit any significant variation with time. However, when averaged across time, HR fell significantly (p less than 0.001) from baseline: -9.1 +/- 2.3 and -15.0 +/- 2.1 b/min for 50 and 100 micrograms DAME, respectively. Tc displayed a nonsignificant, delayed (greater than 2 hr) rise in Tc with the 50 micrograms dose, whereas the 100 micrograms dose caused a significant (p less than 0.001) decline in Tc (from 65-125 min post-injection). NAL injected ICV attenuated the effects of DAME but had no effect on SBP, HR or Tc when injected alone. Systemic injection of DAME (300 micrograms) in one monkey produced a transient decline in SBP (26 mmHg within 2 min) which returned to baseline values 4 min post-injection. HR and Tc were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Autonomic effects of central injections of D-Ala2-Met-enkephalinamide (DAME) in the conscious monkey. 649 24

The effect of naloxone on learned performance reinforced by food was examined in 2 experiments. Male rats were trained to run down a short runway for 5 (45 mg) food pellets per trial and were then shifted either to 1 or 0 pellets. Following such an abrupt reinforcement shift, animals typically show an emotional disruption of performance (Crespi, 1942) referred to as "depression". We examined the postshift depression-effect in groups treated either with saline (SAL) or naloxone (NAL). In experiment 1 NAL groups received a single 10 mg/kg (s.c.) injection prior to each postshift session. When compared with SAL controls, NAL animals showed an exaggerated postshift depression-effect. Furthermore, a single (0.3 mg/kg, s.c.) injection of the enkephalin analog FK 33-824 (D-Ala2, MePhe4, Met-(0)5-o1) produced a dramatic recovery of performance. In the second experiment, these effects were replicated at a low NAL dose (1 mg/kg), which had no direct effect on motor performance. These findings suggest that opiate systems may modulate the incentive motivation that maintains learned performance.
 ...
PMID:Endogenous opioids: naloxone disrupts learned performance in rats. 668 24

The pharmacological actions of Tyr-D-Met(O)-Gly-MePheol (syndyphalin (SD)-25) were compared with those of morphine after systemic administration. The analgesic potency of SD-25 was about 4 times that of morphine when administered s.c. to rats. SD-25 did not exhibit any narcotic antagonist activity. Subcutaneous administration of SD-25 produced a dose-dependent suppression of morphine withdrawal signs in morphine-dependent rats, typical morphine-like jumping in the mouse jumping test, and an increase in spontaneous locomotor activity in mice. These activities were 2-5 times those of morphine. In the anaesthetized dog, intravenous administration of SD-25 produced a 100-1000 times stronger increase in the amplitude of contractions of the jejunum than did morphine, a weaker depression in respiration than morphine, and a slight increase in blood pressure. These effects were reversed by naloxone. These results indicate that SD-25 possesses potent central nervous system actions closely similar to those of morphine, but its effect on blood pressure and respiration was weaker than that of morphine.
 ...
PMID:Analgesic and other pharmacological activities of an enkephalin analogue, syndyphalin (SD)-25. 689 34

Opiate alkaloid and opioid peptide actions on spontaneous neuronal activity and postsynaptic amino acid responsiveness were assessed using intracellular recording techniques applied to murine spinal cord neurons in primary dissociated cell culture. Application of opiates was by superfusion and amino acids by iontophoresis. Glycine and GABA but not glutamate responses were antagonized by the opiate alkaloids. Since opiate effects on glycine and GABA responses were not naloxone-reversible, only weakly stereospecific, and not produced by the opioid peptide [D-Ala2]-Met-enkephalinamide, it is unlikely that these effects were mediated by opiate receptors. Opiate depression of glycine inhibition was correlated with the induction of paroxysmal depolarizations in cultured spinal cord neurons, suggesting that antagonism of inhibitory amino acid transmission may underlie the convulsant actions of high concentrations of the opiate alkaloids.
 ...
PMID:Opiate alkaloids antagonize postsynaptic glycine and GABA responses: correlation with convulsant action. 706 78

The opioid peptides Leu-enkephalin, Met-enkephalin and D-Ala2-Met-enkephalinamide were injected at various concentrations into the neocortex and hippocampus of rats to examine their effects on EEG activity and DC potentials. All three compounds were found to elicit spreading depression (SD) in both structures. Higher doses of Met-enkephalin were required to elicit SD as well as seizure activity. In the hippocampus the wave of SD was frequently preceded by seizure activity which was antagonized by naloxone pretreatment (40 mg/kg i.p.). Naloxone also prevented Leu-enkephalin-induced SD in the neocortex (but not in the hippocampus) and Met-enkephalin-induced SD in the hippocampus (but not in the neocortex). It failed to block SD elicited by D-Ala2-Met-enkephalinamide in both structures. Some of the various reported behavioral effects of intracranial injections of enkephalins could be artefacts of hippocampal and/or cortical spreading depression.
 ...
PMID:Spreading depression induced by microinjection of enkephalins into the hippocampus and neocortex. 722 10

The respiratory effects of Met-enkephalin (900 microgram), D-Ala2-Met-enkephalinamide (10 microgram), and beta-endorphin (10 microgram) were studied and compared in lightly anesthetized cats, after injection into the lateral ventricle and into the pontomedullary subarachnoid space. The 3 peptides injected into the lateral ventricle induced equidepressant effects on respiration, but the duration of action and the involvement of either frequency or tidal volume varied considerably. Met-enkephalin was shorter-acting (45 min) than both D-Ala2-Met-enkephalinamide and beta-endorphin (over 5 h). The depression induced by beta-endorphin was preceded by a long-lasting stimulation of frequency. The effects were antagonized by i.v. naloxone, but the antagonism was not complete in one third of the animals. In the pontomedullary subarachnoid space, beta-endorphin failed to depress respiration significantly whereas Met-enkephalin induced an immediate and short-acting depression (15 min), and D-Ala2-Met-enkephalinamide depressed respiration for 2-4 h in a biphasic pattern. It is concluded that: (1) respiration is depressed by the 3 opiate peptides; (2) the effects of beta-endorphin on respiration, at the dose used in this study, are secondary to other actions on higher brain structures; and (3) Met-enkephalin and D-Ala2-Met-enkephalinamide seem to affect pontomedullary areas located near the ventral surface, although they may also interact with respiratory structures located more deeply in the brain stem.
 ...
PMID:Respiratory effects of beta-endorphin, D-Ala2-met-enkephalinamide, and Met-enkephalin injected into the lateral ventricle and the pontomedullary subarachnoid space. 740 21

The extent to which dietary protein can be minimized by using Met and Lys supplements for market turkeys has been investigated in three experiments involving 2,750 birds. Large White (Nicholas) male turkey poults were fed corn-soybean meal diets of varying protein level to supply Lys from 80 to 120 of NRC (1984) from day-old to 18 wk of age. Performance with diets of 90% NRC Lys was equal to that with diets of higher Lys, provided that SAA were at 100% of NRC. Up to .2% Lys.HCl could be substituted into the 100 or 90% of NRC diets with no depression in performance, suggesting that the other essential amino acids were present in adequate amounts. When turkeys were fed diets of 85% of NRC (1984) Lys, maximum growth and breast meat yield were obtained with supplemental SAA at 100% during 0 to 18 wk of age and Lys at 100% during 12 to 18 wk of age. The requirements for other amino acids were supplied by diets formulated to provide 85% of the Lys requirement from protein. These values were for turkeys subjected to 18 C during final growout; they were not adequate in warmer temperatures.
 ...
PMID:Replacing protein in corn-soybean turkey diets with methionine and lysine. 747 91

A low-frequency stimulus train to the preganglionic input inhibits synaptic transmission in the superior cervical ganglion (SCG) of the cat. The inhibition is blocked by naloxone as well as by selective antagonists at mu and delta opiate receptors, which suggests that the mediator is an endogenous opioid [27,29]. Exogenous opioid peptides, including methionine-enkephalin (Met-Enk), which is present in preganglionic axons of the SCG, inhibit ganglionic transmission by a naloxone-sensitive mechanism. In the present study we test, in the anesthetized cat, whether the naloxone-sensitive synaptic inhibition is mediated by a pre- and/or post-synaptic mechanism. As a test of presynaptic inhibition, we measured the acetylcholine (ACh) released by preganglionic stimulation into the venous effluent of the perfused SCG. As a test of post-synaptic inhibition, we measured the effect of a preganglionic conditioning train on the ganglion cell firing evoked by ganglion-stimulant drugs injected into the arterial supply of the ganglion. In presence of naloxone (3 microM), which blocked the synaptic inhibition, the amount of ACh released by stimulated preganglionic axons did not change. Thus, the endogenous opioid which mediates the naloxone-sensitive inhibition does not act by depressing ACh release. In contrast, the ganglion cell firing evoked by ganglion-stimulant drugs was markedly depressed by a conditioning train, and naloxone blocked the depression, which suggests that the endogenous mediator of the naloxone-sensitive inhibition acts postsynaptically to decrease the excitability of ganglion cells. Exogenous Met-Enk depressed both ACh release by preganglionic stimulation and the firing of ganglion cells evoked by ganglion-stimulant drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The site of the inhibitory action of endogenous opioids in the superior cervical ganglion of the cat. 755 45


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