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)

In pontine slices of the rat brain, the frequency of spontaneous action potentials of locus coeruleus (LC) neurones was recorded extracellularly. Noradrenaline 0.1-100 mumol/l, UK 14,304 0.01-100 nmol/l, [Met5]-enkephalin 1-10,000 nmol/l and [D-Ala2,D-Leu5]enkephalin 0.1-1,000 nmol/l, all depressed the firing rate. Rauwolscine 1 mumol/l antagonized the effects of both noradrenaline and UK 14,304, but potentiated the effects of [Met5]enkephalin and [D-Ala2, D-Leu5]enkephalin. Idazoxan 1 mumol/l acted in a similar manner. Prazosin 1 mumol/l did not change the effects of either noradrenaline or [Met5]enkephalin. Naloxone 0.1 mumol/l antagonized both [Met5]enkephalin and [D-Ala2, D-Leu5]enkephalin, but failed to alter the effects of either noradrenaline or UK 14,304. Rauwolscine, idazoxan and prazosin, all 1 mumol/l, as well as naloxone 0.1 mumol/l, did not influence the firing rate when given alone. Desipramine 1 mumol/l inhibited the discharge of action potentials in a rauwolscine-antagonizable manner. Noradrenaline 10 mumol/l produced the same depression of firing, both in the presence of noradrenaline 1 mumol/l and [Met5]enkephalin 0.03 mumol/l. Likewise, the effect of [Met5]enkephalin 0.3 mumol/l was the same, irrespective of whether it was added to a medium containing [Met5]enkephalin 0.03 mumol/l or noradrenaline 1 mumol/l. The spontaneous activity of LC neurones is inhibited by somatic alpha 2-adrenoceptors and opioid mu-receptors. We suggest that the two receptors interact with each other at a site located between themselves and not in the subsequent common signal transduction system.
 ...
PMID:Blockade of alpha 2-adrenoceptors increases opioid mu-receptor-mediated inhibition of the firing rate of rat locus coeruleus neurones. 198 56

Cross-tolerance to the respiratory depression induced by i.c.v. [D-Ala2,D-Leu5]enkephalin (DADLE) and by s.c., i.c.v. and i.v. morphine was studied in anesthetized rats that had been rendered tolerant to s.c. sufentanil (4 micrograms/h per 7 days). Tolerance induced by i.c.v. sufentanil was also compared during withdrawal and its absence. Tolerance was evaluated by estimation of the changes in both the maximum attained reduction of respiratory frequency (Emax) and the area under the time-course curve for the effects (AUC). In contrast to the failure to develop tolerance, as estimated with the Emax, after i.c.v. sufentanil in the absence of abstinence (tolerance index: 1.1), rats displayed significant degrees of cross-tolerance to i.c.v. morphine (3.6), i.c.v. DADLE (4.3) and s.c. morphine (6.6). No tolerance, however, was obtained to i.v. morphine. Tolerance to i.c.v. sufentanil in non-abstinent rats was not present when the Emax was considered but was when AUC was considered. During withdrawal animals showed tolerance as estimated with both the Emax and AUC. These results complement previous findings and show that the appearance of dissimilar degrees of cross-tolerance to different agonists depends not only on their intrinsic activities but also on their pharmacokinetic properties. These observations, along with the critical influence of withdrawal upon the manifestation of tolerance, support the need to distinguish between the development of the tolerance state and the degree of tolerance that can be expressed under specific conditions.
 ...
PMID:Tolerance to the respiratory actions of opiates: withdrawal tolerance and asymmetrical cross-tolerance. 213 80

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.
 ...
PMID:Opioid antagonist modulation of murine neuroblastoma: a profile of cell proliferation and opioid peptides and receptors. 254 Aug 73

Single-unit extracellular recording was carried out in rats to characterize the effects of dynorphin and several structurally related peptides on hippocampal pyramidal cell activity. Dynorphin, applied electrophoretically or by pneumatic pressure, produced a dose-dependent depression of both spontaneous and glutamate-evoked discharge in a majority (63%) of CA1 and CA3 cells tested. In addition, a small number of cells in both cellular fields responded to the peptide with a prolonged elevation in firing. The inhibitory effects of dynorphin were not blocked by naloxone. Moreover, administration of des-tyrosine-dynorphin depressed the firing of pyramidal cells in a manner similar to that of the parent compound. Ethylketocyclazocine produced a mixed pattern of excitatory and inhibitory effects, whereas naloxone-sensitive elevations in firing were most often observed with the application of dynorphin-(1-8). Application of [Leu5]enkephalin produced only facilitations in pyramidal cell firing. The possibility is raised that biologically significant non-opiate actions, in addition to potent opiate-mediated effects, may occur upon release of pro-dynorphin peptides in the hippocampus.
 ...
PMID:Electrophysiological effects of dynorphin peptides on hippocampal pyramidal cells in rat. 285 95

In the mouse isolated vas deferens the amplitude of excitatory junction potentials (e.j.p.s) recorded intracellularly from smooth muscle cells varied with the strength of stimulation. Receptor type selective opioids were tested in this preparation. The mu-agonist normorphine (2,000 nmol/l) reduced the amplitude of e.j.p.s and shifted the stimulus-response curve in a parallel way to the right. By contrast, the kappa-agonist U-50488 (1,000 nmol/l) and the delta-agonist [D-Ala2,D-Leu5]-enkephalin (2 nmol/l) caused a non-parallel shift of the curve. In addition, opioids having a lower selectivity for one type of receptor were also used. The preferential kappa-agonists ethylketocyclazocine (40 nmol/l) and dynorphin A1-13 (100 nmol/l) produced parallel and non-parallel shifts, respectively. Thus, normorphine and ethylketocyclazocine were more effective in depressing e.j.p.s evoked by low intensities of stimulation than those evoked by high intensities of stimulation. U-50488, dynorphin A1-13 and [D-Ala2,D-Leu5]-enkephalin caused an equal depression of e.j.p.s evoked by either intensity of stimulation. The preferential mu- and delta-antagonists naloxone (1,000 nmol/l) and ICI 154129 (10,000 nmol/l), reversed the action of the respective agonists normorphine and [D-Ala2, D-Leu5]-enkephalin. In addition, ICI 154129 (10,000 nmol/l) reversed the action of dynorphin A1-13, as well. The preferential kappa-antagonist MR-2266 (1,000 nmol/l) prevented the effect of both ethylketocyclazocine and U-50488. It is concluded that under the conditions of these experiments normorphine and ethylketocyclazocine acted at mu-, U-50488 at kappa-, and dynorphin A1-13 and [D-Ala2,D-Leu5]-enkephalin at delta-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Differential effect of stimulation strength in mouse vas deferens on inhibition of neuroeffector transmission by receptor type selective opioids. 286 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.
 ...
PMID:Characterization of opioid receptors in the cat carotid body involved in chemosensory depression in vivo. 287 62

Pretreating rats 24 hr earlier with naloxonazine (10 mg/kg i.v.) virtually eliminates the analgesic response observed with morphine at 3.5 mg/kg (i.v.) and significantly reduces the elevation in tail-flick latencies seen with higher morphine doses. Full dose-response curves show a 4-fold shift to the right (P less than .001) following naloxonazine treatment. At 3.5 mg/kg (i.v.), morphine depresses respiratory function, as determined by arterial blood gas (pO2, pCO2 and pH) measurements. Unlike analgesia, prior treatment of rats with naloxonazine does not alter the respiratory depressant actions of morphine. This inability of naloxonazine to antagonize the respiratory depressant actions of morphine is supported by full dose-response curves. Thus, prior treatment of rats with the mu-1-selective antagonist naloxonazine selectively antagonizes analgesia without affecting respiratory depression, implying different receptor mechanisms for the analgesic and respiratory depressant effects of morphine. Further comparisons of the analgesic and respiratory depressant effects of morphine and two opioid peptides, metkephamid and D-Ala2-D-Leu5-enkephalin, strongly suggest the involvement of mu-2 rather than delta mechanisms in opioid respiratory depression.
 ...
PMID:Separation of opioid analgesia from respiratory depression: evidence for different receptor mechanisms. 298 12

Exposure of fetal mouse spinal cord-ganglion explants to morphine (greater than 0.1 microM) results in naloxone-reversible, dose-dependent depression of sensory-evoked dorsal-horn synaptic-network responses within a few minutes. After chronic opiate exposure (1 microM) for 2-3 days, these dorsal cord responses recover and can then occur even in greater than 10 microM morphine. In the present study, when naive explants were treated with forskolin (10-50 microM)--a selective activate activator of cyclase (AC)--for 10-30 min prior to and during exposure to morphine (0.1-0.3 microM) or D-Ala2-D-Leu5-enkephalin (0.03-0.1 microM), the usual opioid depressant effects on dorsal-horn responses generally failed to occur (10-30 min tests). Dibutyryl cyclic AMP (10 microM) or the more lipid-soluble analog, dioctanoyl cyclic AMP (0.1 mM), produced a similar degree of subsensitivity to opiates as 10 microM forskolin. With high levels of forskolin (50 microM), even concentrations of morphine up to 1-10 microM were far less effective in depressing cord responses. These effects of exogenous cAMP analogs and forskolin on cord-ganglion explants are probably both mediated by increases in intracellular cAMP. The marked decrease in opioid sensitivity of cAMP or forskolin-treated cord-ganglion explants provides significant electrophysiologic data compatible with the hypothesis that neurons may develop tolerance and/or dependence during chronic opioid exposure by a compensatory enhancement of their AC/cAMP system following initial opioid depression of AC activity. Previous evidence relied primarily on behavioral tests and biochemical analyses of cell cultures. It will be of interest to determine if dorsal-horn tissues of cord-ganglion explants do, in fact, develop increased AC/cAMP levels as they express physiologic signs of tolerance during chronic exposure to opioids.
 ...
PMID:Cyclic AMP or forskolin rapidly attenuates the depressant effects of opioids on sensory-evoked dorsal-horn responses in mouse spinal cord-ganglion explants. 301 Nov 95

Excitatory junction potentials (e.j.p.s) evoked by nerve stimulation were recorded from muscle cells of the rabbit isolated mesenteric artery. At 0.03 Hz the e.j.p. amplitudes were stable. When a train of fifteen pulses was applied at 0.25 Hz or at higher frequencies (0.5, 1 and 2 Hz), e.j.p.s showed an initial facilitation followed by depression. [Met5]enkephalin 0.1 and 1 mumol/l, [D-Ala2,D-Leu5]enkephalin 0.1 and 1, but not 0.01 mumol/l, and [D-Pen2, L-Pen5]enkephalin 3 mumol/l all depressed the e.j.p.s evoked by trains of fifteen pulses at 1 Hz. When more than one concentration was used ([Met5]enkephalin, [D-Ala2,D-Leu5]enkephalin), the inhibition was concentration dependent. It was always greater for the first few e.j.p.s than for the later ones in a train. [Met5]enkephalin 1 mumol/l reduced the first e.j.p. at 1 Hz and the e.j.p.s evoked by 0.03 Hz to a similar extent. The inhibitory effect of [Met5]enkephalin 1 mumol/l on e.j.p.s persisted in the presence of yohimbine 0.3 mumol/l. Naloxone 1 mumol/l did not interfere with the effect of [Met5]enkephalin 1 mumol/l. Naloxone 10 mumol/l depressed some e.j.p.s and prevented the inhibition by [Met5]enkephalin 1 mumol/l. Neither ICI 154129 10 mumol/l nor ICI 174864 0.3 mumol/l had any effect of their own and both compounds antagonized the action of [Met5]enkephalin 1 mumol/l. Normorphine 10 mumol/l, fentanyl 1 mumol/l, ethylketocyclazocine 0.1 mumol/l, and dynorphin A(1-13) 1 mumol/l were all ineffective. Ethylketocyclazocine 1 mumol/l did not change the e.j.p.s either, but antagonized [Met5]enkephalin 1 mumol/l. [Met5]enkephalin 1 mumol/l failed to influence both the resting membrane potential of the muscle cells and the depolarizing effect of noradrenaline 3 and 30 mumol/l. We suggest that the axon terminals of post-ganglionic sympathetic neurones in the rabbit mesenteric artery possess opioid delta-, but not mu- or kappa-receptors. The activation of presynaptic delta-receptors inhibits the release of the neuroeffector transmitter. There is no evidence for any effect of co-released endogenous opioid peptides under our experimental conditions.
 ...
PMID:Presynaptic opioid delta-receptors in the rabbit mesenteric artery. 303 Dec 83

In unanesthetized dogs prepared with chronic tracheostomies and chronically implanted intrathecal (IT) catheters having openings in the cisterna magna and lumbar region, lumbar IT injection of D-Ala2-D-Leu5-enkephalin (DADL, 1-10 mg) and morphine (3-30 mg) produced a dose-dependent depression of the slope of the CO2 response function (minute expired volume [VE] vs. end-tidal [ET] CO2) as investigated by a modified Read rebreathing technique. The maximum depression occurred less than 3 h after IT injection of either agent and lasted as long as 12 h. The depression was totally reversed by naloxone (0.4 mg/kg, iv). Naloxone alone had no effect on ventilatory function. After 10 mg DADL, there was no significant change in heart rate (HR), mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP), cardiac output (CO), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), or PaO2 during the 3 h postinjection. In contrast, PaCO2 was significantly elevated and pH significantly decreased (P less than 0.05). Naloxone administration after high-dose IT DADL resulted in a doubling of MABP, MPBP, CO, and SVR that lasted approximately 20 min. In concurrently measured cisternal cerebrospinal fluid (CSF) levels, both morphine and DADL displayed peak levels by 30-60 min. The lumbar CSF clearance curves for both agents were fitted with a two-compartment intravenous bolus model. The t 1/2 alpha was 13.8 +/- 3.6 min for DADL and 9.4 +/- 1.6 min for morphine (mean +/- SE). The t 1/2 beta was 101.3 +/- 17.7 min for DADL and 116.7 +/- 27.9 min for morphine.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cardiorespiratory effects and kinetics of intrathecally injected D-Ala2-D-Leu5-enkephalin and morphine in unanesthetized dogs. 309 39


1 2 3 Next >>