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 respiratory depression induced by two mu-opiate agonists morphine and Tyr-D-Ala-Gly-N-Me-Phe-Met(O)-ol (FK-33824), and two delta-agonists Tyr-D-Ala-Gly-Phe-D-Leu (DADLE) and Tyr-D-Ser-Gly-Phe-Leu-Thr (D-Ser2-Thr6) was studied in rats by using the intracerebroventricular route. The four opioids caused a dose-dependent depression of respiratory frequency down to apnea but high doses of morphine elicited motor activation and seizure activity. FK-33824 was the most potent, followed by DADLE, D-Ser2-Thr6 and morphine. The in vivo apparent pA2 values were determined for naloxone against FK-33824, DADLE and D-Ser2-Thr6. The pA2 value of naloxone interacting with the mu-agonist FK-33824 was significantly lower than those obtained against the two delta-agonists. It is proposed that different types of opiate receptors are involved in the opiate-induced respiratory depression.
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PMID:Interaction of naloxone with mu- and delta-opioid agonists on the respiration of rats. 630 57

To further investigate the role of opioid peptides and specific opiate receptor subtypes in central cardiovascular regulation by hindbrain nuclei, mu (D-Ala2,MePhe4,Gly-ol5 enkephalin, DAGO), delta (D-Ala2,D-Leu5 enkephalin, DADL) or kappa (MRZ 2549) agonists were microinjected into hindbrain nuclei of spontaneously or artificially respired, pentobarbital-anesthetized rats. In the nucleus tractus solitarius (NTS), DAGO and DADL (0.3 nmol) elicited pressor responses and tachycardia. MRZ (3.0-16 nmol) depressed blood pressure in spontaneously breathing rats, but accelerated heart rate in artificially ventilated animals. Blood pressure and heart rate of spontaneously breathing animals were not altered following nucleus ambiguus (NA) injection of DAGO or DADL (0.3 nmol), but were elevated in artificially respired animals; MRZ (3.0-10 nmol) injected into the NA depressed blood pressure in both groups. These data suggest that in the absence of respiratory depression, NTS and NA mu receptors mediate pressor responses and tachycardia; kappa receptors in the NA mediate a decrease in blood pressure but cardioacceleration in the NTS.
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PMID:Differential cardiovascular effects mediated by mu and kappa opiate receptors in hindbrain nuclei. 631 99

The involvement of different opiate receptor subtypes in opiate-induced respiratory depression was studied in the unanaesthetized rat. Synthetic opioid agonists, specific for mu or delta receptors, were administered intraperitoneally in freely moving rats while respiratory parameters were recorded by means of the whole body plethysmographic method. TRIMU-4 (Tyr-D-Ala-Gly-NH-CH(CH3)-CH2-CH(CH3)2), a specific agonist of the mu receptor, reduced the tidal volume and did not change the respiratory frequency. DSLET (Tyr-D-Ser-Gly-Phe-Leu-Thr), a relatively specific agonist of the delta receptor subtype, reduced respiratory frequency and was significantly less effective on tidal volume than was TRIMU-4. It is concluded that the respiratory depression occurring after the administration of opiates in clinical practice is a dual complementary effect involving mu and delta receptors.
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PMID:Different effects of mu and delta opiate agonists on respiration. 632 18

The respiratory and cardiovascular effects of the highly selective mu opioid agonist, D-Ala2, MePhe4, Gly- ol5 enkephalin ( DAGO ) and the relatively selective delta agonist, D-Leu5 enkephalin (DADL) were compared following injection (0.1 microliter) into the nucleus ambiguus (NA) of spontaneously-breathing and artificially-respired, pentobarbital-anesthetized rats. In non-ventilated animals, the opioids elicited dose-related (3 X 10(-11) -3 X 10(-9) M), naloxone-reversible depression of respiratory rate (RR) without altering the tidal volume. Mean arterial pressure (MAP) was unchanged at small doses and decreased at the largest dose; heart rate (HR) was unchanged. In artificially-respired animals, both peptides elicited dose-related, naloxone-reversible increases in mean arterial pressure and heart rate; DAGO was significantly more potent than DADL (P less than 0.01). Given the relative potency and selectivity of the opioids tested, these findings are consistent with the conclusion that mu receptors may selectively mediate the respiratory and cardiovascular actions of opioids in an important brain stem cardiorespiratory center in the rat. Moreover, these data indicate the importance of respiratory effects on the cardiovascular activity of centrally administered opioids.
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PMID:Selective cardiorespiratory effects mediated by mu opioid receptors in the nucleus ambiguus. 632 52

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.
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PMID:A comparative study in rats of the respiratory depression and analgesia induced by mu- and delta-opioid agonists. 637 10

The influence of synthetic thyrotropin-releasing hormone (TRH) on locomotion, on the effects of analgetics, learning and memory, electrical activity of hypothalamic neurons, blood pressure, and cerebral circulation have been studied. TRH increases the spontaneous motility and potentiates the stimulating effect of amphetamine and apomorphine. It also antagonizes the decrease of motility induced by tetrabenazine in all these tests. TRH exhibits the similarity to antidepressants. TRH antagonizes the effects of morphine and Tyr-D-Ala-Gly-Phe-(NO2)-NH2, especially in respect of respiratory depression experiments made on rats and rabbits. TRH facilitates the learning in active avoidance paradigme, diminishes the degree of retrograde amnesia evoked by maximal electroconvulsive shock. The latter effect suggests that TRH can be considered as a substance having some signs of nootropic activity. TRH seems to interact with central M-cholinergic system. This is evidenced by the ability of atropine to diminish the excitatory effect of TRH applied microiontophoretically to single neurons of the lateral hypothalamus. TRH elevates blood pressure and volume velocity of the cerebral circulation in normotensive animals and recovers the hemodynamics during hemorrhagic hypotension. The spectrum and mechanism of TRH pharmacological activity are discussed. The data suggest that TRH may be of interest for clinical trials.
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PMID:[Pharmacology of thyroliberin]. 641 82

Eighty-five samples from fifteen different legume seed lines generally available in the UK were examined by measurements of their net protein utilization by rats and by haemagglutination tests with erythrocytes from a number of different animal species. From these results the seeds were classified into four broad groups. Group a seeds from most varieties of kidney (Phaseolus vulgaris), runner (Phaseolus coccineus) and tepary (Phaseolus acutifolius) beans showed high reactivity with all cell types and were also highly toxic. Group b, which contained seeds from lima or butter beans (Phaseolus lunatus) and winged bean (Psophocarpus tetragonolobus), agglutinated only human and pronase-treated rat erythrocytes. These seeds did not support proper growth of the rats although the animals survived the 10 d experimental period. Group c consisted of seeds from lentils (Lens culinaris), peas (Pisum sativum), chick-peas (Cicer arietinum), blackeyed peas (Vigna sinensis), pigeon peas (Cajanus cajan), mung beans (Phaseolus aureus), field or broad beans (Vicia faba) and aduki beans (Phaseolus angularis). These generally had low reactivity with all cells and were non-toxic. Group d, represented by soya (Glycine max) and pinto (Phaseolus vulgaris) beans, generally had low reactivity with all cells but caused growth depression at certain dietary concentrations. This growth depression was probably mainly due to antinutritional factors other than lectins. Lectins from group a seeds showed many structural and immunological similarities. However the subunit composition of the lectin from the tepary bean samples was different from that of the other bean lectins in this or any other groups.
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PMID:A survey of the nutritional and haemagglutination properties of legume seeds generally available in the UK. 661 58

The effect of a highly active agonistic analogue analogue of LH-RH on testicular weight an pituitary gonadotropin levels was studied in male rats previously treated with estrogens. These steroids induced a considerable depression of testicular weight. In the first experiment the treatment with a high dose (4 microgram daily) of D-Ala-6-des-Gly-10-LH-RH-ethylamide, the superactive analogue used, further depressed testicular weight and pituitary gonadotropins. In a second experiment, the treatment with lower doses (100 ng daily) of the analogue in estrogen-treated rats induced a slight but significant stimulatory effect on testicular weight and pituitary FSH content. In the third experiment none of the three doses of the analogue used (1, 10, or 100 ng daily) modified testicular weight when the treatment was started shortly after the administration of estrogens. It is concluded that, according to the dose of the analogue used, it is possible to observe inhibitory or stimulatory effect on testes and pituitary gonadotropin levels.
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PMID:Effects of a superactive analogue of LH-RH on the hypothalamo-pituitary-testicular axis in male rats pretreated with estrogens. 678 60

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.
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PMID:Analgesic and other pharmacological activities of an enkephalin analogue, syndyphalin (SD)-25. 689 34

Parallel electrophysiological and neurochemical studies of development are reported for mouse spinal cord cell cultures. The time course of electrical activity and the stage-dependent effects of tetrodotoxin on levels of the neuronal enzyme choline acetyltransferase were compared to establish the presence of spontaneous electrical activity at a time when tetrodotoxin adversely affects development. The extracellular patch electrode makes it possible to examine the ongoing electrical activity of the small cells present in young cultures. A rapid increase in spontaneous electrical activity during the first 2 weeks in culture was found to correlate closely with the onset of tetrodotoxin-induced depression of choline acetyltransferase activity, supporting the idea that ongoing electrical activity plays a role in neuronal development. The development of inhibitory synaptic activity occurs gradually throughout the period of culture, whereas excitatory synaptic activity and action potentials develop in unison, reaching maximal levels during the 2nd week in culture. For all cultures tested, ranging in age from 9 to 45 days old, acute bath application of gamma-aminobutyric acid (GABA) abolished spontaneous electrical activity. Glycine is relatively ineffective in abolishing spontaneous activity in young cultures which have few inhibitory postsynaptic potentials (IPSPs), but glycine becomes as effective as GABA at a later stage of development. This suggests rather different timetables of development for GABA and glycine receptors, with glycine receptors developing in parallel with IPSPs.
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PMID:Electrical development in spinal cord cell culture. 705 Mar 10


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