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)

High-threshold (HVA) Ca2+ channels of human neuroblastoma IMR32 cells were effectively inhibited by noradrenaline. At potentials between -20 mV and +10 mV, micromolar concentrations of noradrenaline induced a 50%-70% depression of HVA Ba2+ currents and a prolongation of their activation kinetics. Both effects were relieved at more positive voltages or by applying strong conditioning pre-pulses (facilitation). Facilitation restored the rapid activation of HVA channels and recruited about 80% of the noradrenaline-inhibited channels at rest. Re-inhibition of Ca2+ channels after facilitation was slow (tau r 36-45 ms) and voltage-independent between -30 mV and -90 mV. The inhibitory action of noradrenaline was dose-dependent (IC50 = 84 nM), mediated by alpha 2-adrenergic receptors and selective for omega-conotoxin-sensitive Ca2+ channels, which represent the majority of HVA channels expressed by IMR32 cells. The action of noradrenaline was mimicked by intracellular applications of GTP[gamma S] and prevented by GDP[beta S] or by pre-incubation with pertussis toxin. The time course of noradrenaline inhibition measured during fast application (onset) and wash-out (offset) of the drug were independent of saturating agonist concentrations (10-50 microM) and developed with mean time constants of 0.56 s (tau on) and 3.6 s (tau off) respectively. The data could be simulated by a kinetic model in which a G protein is assumed to modify directly the voltage-dependent gating of Ca2+ channels. Noradrenaline-modified channels are mostly inhibited at rest and can be recruited in a steep voltage-dependent manner with increasing voltages.
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PMID:Voltage-dependent noradrenergic modulation of omega-conotoxin-sensitive Ca2+ channels in human neuroblastoma IMR32 cells. 133 78

Unilateral olfactory deprivation in the rat profoundly modifies olfactory bulb anatomy, chemistry and function. The present report examined the time-course of the functional effects of unilateral deprivation on inhibition in the olfactory bulb using paired-pulse stimulation of the lateral olfactory tract and olfactory nerve. In addition, an attempt was made to correlate these physiological measures with olfactory bulb dopamine and norepinephrine levels and tyrosine hydroxylase immunoreactivity. Deprivation from postnatal day 1 to postnatal day 20 or postnatal day 40 significantly enhanced lateral olfactory tract paired-pulse depression, while late onset deprivation (postnatal day 20) had no effect. Olfactory nerve paired-pulse depression was enhanced by 40 days of deprivation regardless of the age at onset. The time-course of these deprivation-induced physiological changes did not correlate well with reductions in dopamine. Dopamine levels were reduced in all deprivation conditions by 70-80% compared with control bulbs. Norepinephrine content was slightly elevated in deprived bulbs. These results suggest that early olfactory deprivation modifies olfactory bulb synaptic activity and further, as with other sensory systems, these effects are age and duration dependent.
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PMID:Functional consequences of unilateral olfactory deprivation: time-course and age sensitivity. 135 86

From a total of 81 patients on maintenance hemodialysis who underwent coronary angiography, 8 patients fulfilled the criteria: significant coronary artery disease, hematocrit less than 27%, reproducible (ECG) positive treadmill test, no disturbance of repolarization in ECG at rest. Exercise stress testing was performed at a hematocrit of 25 +/- 2% and following erythropoietin therapy at a hematocrit of 34 +/- 0.5%. Symptom-limited exercise performance increased in all patients (1.10 +/- 0.3 W/kg b.w. vs. 1.44 +/- 0.31 W/kg b.w., p less than 0.01) as well as exercise duration (489 vs. 362 s, p +/- 0.01). ST segment depression during maximal exercise was reduced from a mean of 2.1 to 0.4 mm (p less than 0.01). It is concluded that amelioration of renal anemia by erythropoietin in dialysis patients with significant coronary artery disease reduces exercise-induced myocardial ischemia.
Nephron 1992
PMID:Effect of erythropoietin on ischemia tolerance in anemic hemodialysis patients with confirmed coronary artery disease. 143 8

A disease-specific questionnaire was developed for patients receiving chronic hemodialysis by interviewing patients to determine which aspects of their quality of life were adversely affected by their disease. The final questionnaire contained 26 questions in five dimensions (physical symptoms, fatigue, depression, relationships with others, frustration). The questionnaire demonstrated construct validity when compared with the Sickness Impact Profile, time trade-off technique and an exercise stress test. It was reproducible in stable, placebo-treated patients (correlation coefficient 0.85-0.98 for the 5 dimensions). It was more responsive than other measures in detecting an improvement with erythropoietin therapy in a randomized, placebo-controlled trial. This questionnaire should be useful for the assessment of the effect of various interventions upon the quality of life of hemodialysis patients.
Nephron 1992
PMID:A disease-specific questionnaire for assessing quality of life in patients on hemodialysis. 156 82

In order to gain insight into the mechanism of the autoinhibition of noradrenaline release, the present study explores the effects of substances acting at various adrenoceptor-subtypes on voltage-activated Ca2+ currents. Experiments were carried out on cultured embryonic chick sympathetic neurons using the patch clamp technique. Ca2+ currents associated with a (fully activating) depolarizing 150 ms voltage step to 0 mV were reduced by noradrenaline and the two alpha 2-adrenoceptor agonists UK 14,304 and clonidine, predominantly during the early phase of activation. We quantified these effects by measuring Ca2+ current amplitudes in the absence and presence of substances 10 ms after the beginning of the depolarization. Noradrenaline effects were maximal at 5 mumol/l, causing a 28% depression of the current. Half-maximal effects (IC50) were apparent at 0.7 mumol/l. UK 14,304 was equipotent to noradrenaline (IC50: 0.5 mumol/l; maximal effect: 26% depression). Clonidine, while active in the same range of concentration (IC50: 0.6 mumol/l), had a smaller maximal effect (20% depression). Methoxamine and isoprenaline, on the other hand, did not significantly reduce the Ca2+ current at 10 mumol/l. The noradrenaline-induced inhibition was attenuated by yohimbine (1 mumol/l). Neither prazosin (1 mumol/l) nor propranolol (1 mumol/l) interfered with the effect of noradrenaline. These results indicate a reduction of Ca2+ influx via alpha 2-adrenoceptors and suggest that the autoreceptor-mediated inhibition of transmitter release in embryonic chick sympathetic neurons operates through the modulation of Ca2+ channels.
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PMID:Modulation of calcium currents via alpha 2-adrenoceptors in embryonic chick sympathetic neurons. 168 90

The purpose of this article is to give the clinician not proficient in biochemistry an understanding of the biochemical research data on neurotransmitters and suicide. This literature review reports the current findings on serotonin (5-HT), dopamine (DA), and norepinephrine (NE) as possible biochemical markers of depression and suicide. In conjunction with known environmental and behavioral indicators of suicide, neurotransmitter balance could be a factor in determining the severity of depression and the possible suicidal ideation in patients. Numerous studies have been performed on the monoamines: Serotonin, Dopamine and Norepinephrine, neurotransmitters that innervate parts of the spinal cord and all areas of the brain. Studies appear to suggest a relationship among monoamine levels, depression, and suicide. Significantly low levels of serotonin and the neurotransmitter metabolite (5-HIAA) may be correlated with suicidal behavior.
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PMID:Monoamines: biochemical markers of suicide? 168 24

We have investigated the effect of an exogenous lactate load given during machine haemofiltration treatment in 22 patients with acute renal failure and 12 patients with chronic renal failure, without any overt evidence of liver disease. Hyperlactataemia occurred in all patients, but the expected changes in acid base status, an increase in bicarbonate and a reduction in arterial hydrogen ions were observed in less than 40% of the treatments in the acute renal failure group. Ultrafiltrate losses of lactate and bicarbonate could not alone explain the changes in acid-base status. There was a positive correlation between the increase in arterial lactate and hydrogen ion concentrations, r = 0.52, p less than 0.01. Lactate accumulation in patients at, or close to, their threshold for lactate utilisation may result in further depression of cardiac function and peripheral lactate utilisation. Hyperlactataemia due to use of lactate-based dialysis/haemofiltration solutions in critically ill patients may result in a worsening of the acid-base status, and arterial pH should be monitored so that bicarbonate solutions can be substituted if the changes are progressive.
Nephron 1991
PMID:Hyperlactataemia and metabolic acidosis during haemofiltration using lactate-buffered fluids. 175 38

Norepinephrine (NE) and epinephrine (E) responses to upright posture were investigated in 25 patients with orthostatic hypotension due to brainstem ischemic lesions and in 25 control subjects. In controls the postural stimulus induced constantly a rise in NE urinary excretion and a reduction in E excretion, while in patients with orthostatic hypotension it caused a depression in NE urinary excretion and a rise in E urinary excretion; the last alteration was noticed in all but one patient. The E discharge induced by posture in patients with orthostatic hypotension may be involved in the reduction of vascular peripheral resistance and then in postural fall of blood pressure displayed by such patients.
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PMID:Norepinephrine and epinephrine responses to postural stimulus in orthostatic hypotension due to brainstem ischemic lesions. 186 28

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.
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PMID:Blockade of alpha 2-adrenoceptors increases opioid mu-receptor-mediated inhibition of the firing rate of rat locus coeruleus neurones. 198 56

1. Norepinephrine (NE) and clonidine produce a phasic, dose-dependent contraction of the isolated guinea-pig terminal ileum. 2. The effect of NE was blocked by prazosin which produced a parallel rightward shift of the concentration-effect curve to NE, with a significant depression of maximum effects. 3. Yohimbine and indomethacin noncompetitively blocked, whereas practolol potentiated, the contractile effect of NE. 4. The contractile effect of clonidine was not antagonized by indomethacin or atropine. 5. These results suggest that the isolated guinea-pig terminal ileum has excitatory receptors sensitive to clonidine stimulation and excitatory alpha receptors sensitive to blockade by prazosin, and that the activation of the latter may be related to the activation of endogenous prostaglandin synthesis.
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PMID:Study of the contraction induced by norepinephrine and clonidine in the isolated guinea-pig ileum. 205 Feb 93


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