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 effects of iontophoretically applied Na+-, K+-dependent adenosinetriphosphatase (Na+,K+-ATPase) (EC 3.6.1.3) inhibitors (ouabain, digitoxin, digitoxigenin, strophanthin K, strophanthidin, thevetin A and B, ethacrynate, and harmaline) on the depression of rat cerebral cortical neurones by noradrenaline, 5-hydroxytryptamine, and histamine have been studied. The inhibitors antagonized depressions of spontaneously active neurones evoked by these amines, but not those evoked by gamma-aminobutyric acid, adenosine, adenosine 5'-monophosphate, or calcium. The antagonistic potencies of the various inhibitors appeared to be proportional to their known potencies as inhibitors of Na+, K+-ATPase. The data therefore support the hypothesis that amines depress central neurones by activating an electrogenic sodium pump.
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PMID:Antagonism of biogenic amine-induced depression of cerebral cortical neurones by Na+, K+-ATPase in inhibitors. 14 20

Effects of vanadate on ouabain binding and inhibition of sodium and potassium adenosine triphosphatase (Na+ + K+)-ATPase) were investigated under various ionic conditions. 1. Vanadate facilitated ouabain binding to (Na+ + K+)-ATPase in the presence of Mg2+ and this facilitation was partially reversed by catechol. 2. Vanadate antagonized the ability of high concentrations of NaCl to inhibit ouabain binding in the presence of magnesium. 3. Ouabain binding to the vanadate-enzyme complex, formed from magnesium and vanadate, was more sensitive to depression by potassium than that to the phosphoenzyme formed from magnesium and inorganic phosphate. 4. Preincubation of (Na+ + K+)-ATPase with vanadate in the presence of magnesium initially formed a potassium-insensitive complex as shown by a rapid initial rate of ouabain binding. However, within 5 min potassium overcame the vanadate potentiation of ouabain binding regardless of the order in which it was added to the reaction mixture. 5. Under conditions of enzyme turnover, vanadate failed to antagonize the inhibitory power of ouabain despite the presence of a high concentration of potassium. This suggests a possible relationship between the sensitivity of the sodium pump in various tissues to the cardiac glycosides and intracellular vanadate concentrations.
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PMID:Effects of vanadate on ouabain binding and inhibition of (Na+ + K+)-ATPase. 22 60

Coma and other neurologic abnormalities are present in patients with either diabetic ketoacidosis (DKA) or nonketotic coma (NKC), and the cause of such phenomena are not known. Patients with NKC also manifest seizures and focal neurologic changes. Treatment of diabetic coma with insulin may induce cerebral edema by as yet undefined mechanism(s). In patients with DKA, cerebral oxygen utilization is impaired, and there is hyperviscosity of the blood. A substantial part of the brain's energy source is derived from ketones, which in themselves can depress sensorium. Extracellular hyperosomolality is present, which may also contribute to the genesis of coma. In addition, most ketoacidotic patients have associated medical conditions, which may further impair consciousness. Biochemical changes in the brains of animals with DKA include impairment of both phosphofructokinase activity and pyruvate oxidation, and accumulation of citrate. The net effect upon sensorium in ketoacidotic patients probably represents the interaction of most of the above factors and differs markedly among individuals. Patients with NKC manifest not only depression of sensorium, but also focal motor seizures, hemiparesis, and other neurologic changes, such as aphasia, hypereflexia, sensory defects, autonomic changes, and brainstem dysfunction. Most of the aforementioned changes revert to normal after correction of hyperosomolality. Gamma amino butyric acid, which has been shown to elevate the seizure threshold, is normal in brains of ketoacidotic animals, but may be low in nonketotic coma. Also, hyperosomolality per se may produce seizures. Cerebral edema may complicate the treatment of either DKA or NKC. The available experimental evidence suggests that many of the commonly held theories for the production of such brain swelling probably do not occur. There is no breakdown of the sodium pump, sorbitol or fructose do not accumulate in brain, and brain glucose is only about 25 percent of that in plasma; Cerebral edema is probably produced largely by a direct action of insulin on brain at a time when plasma glucose is approaching normal values. Cerebral edema can thus theoretically be avoided by stopping insulin when plasma glucose has been lowered to values approaching normal.
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PMID:Neurologic manifestations of diabetic comas: correlation with biochemical alterations in the brain. 80 37

Extracellular potassium activity, [K+]0, was continuously measured using potassium specific microelectrodes in the cerebral cortex of cats before and after hypoxic or anoxic insults. Two patterns of [K+]0 increase were seen. A slow, linear rise occurred during hypoxia and hypothermia and was correlated with changes in mean blood pressure (B/P). A fast, complex, exponential rise resembling spreading depression occurred during anoxia and was unassociated with B/P changes. The fall of [K+]0 after reversal of the insult was described by a single exponential function with rate constants from 0.009 to 0.0194 sec-1. It is suggested that the linear rise is primarily a result of sodium pump inhibition and that the exponential rise is due to a superimposed sudden increase in cell membrane permeability perhaps secondary to transmitter release. The kinetics of the fall of [K+[0 is consistent with the normalization of the sodium and potassium gradients across the cell membranes secondary to Na+-K+ATPase activity.
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PMID:The kinetics of extracellular potassium changes during hypoxia and anoxia in the cat cerebral cortex. 84 9

Postexcitatory depression (PED) and adaptation were examined in slowly adapting aortic baroreceptors of normotensive rats (NTR) and spontaneously hypertensive rats (SHR); an aortic arch-aortic nerve preparation in vitro was used. PED was elicited either mechanically by employing single or double pressure steps, or electrically by antidromic stimulation of the aortic nerve. During PED the axon of the receptor was capable of conducting action potentials and the receptor itself could respond to increased pressures. The relationship between duration of PED and number of impulses preceding it was hyperbolic. In NTR's and SHR's PED was abolished by ouabain or solutions containing no potassium, neither of which affected the steady state pressure-volume relationship of the aorta. These interventions, which are known to block electrogenic pumps, also lowered the pressure threshold and increased the curvature of the steady state pressure-frequency curve. Furthermore, lithium, another agent that blocks electrogenic pumps, also abolished PED. Thus, PED is attributed mainly to an electrogenic sodium pump which operates normally in baroreceptors. We found that adaptation from peak transient to steady state frequency did not appear to be altered significantly when the pump was blocked. Blockage of the pump by ouabain is responsible for the baroreceptor reflex effects elicited by this drug. We conclude that resetting and reduced sensitivity in SHR baroreceptors are not attributed to significant differences in electrogenic pump activity.
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PMID:An electrogenic sodium pump and baroreceptor function in normotensive and spontaneously hypertensive rats. 96 33

By Ussing's flux chamber method the effect of ATP and acetylcholine (ACh) on the sodium transport was studied in bullfrog colon. The results obtained are as follows; 1. ATP added to the mucosal medium caused biphasic changes in the transmural potential difference (P.D.) and short-circuit current (S.C.C.), although serosal ATP was ineffective. After an initial rapid and transient rise, both the P.D. and S.C.C. increased in parallel to reach a peak in about 10 min suggesting that the tissue conductance is little affected by ATP. Addition of ouabain to the serosal fluid depressed both the P.D. and S.C.C. and abolished the electrical responses to ATP. The application of ouabain to the mucosal side did not cause any significant depression. These results can be explained in terms of stimulation of sodium pump by ATP added to the mucosal medium. 2. ACh added to either the mucosal or the serosal medium caused increased in the P.D. and the S.C.C. The serosal application was more effective than the mucosal application. The increase in S.C.C. was more remarkable than that in the P.D., indicating an increase in the tissue conductance. It is suggested that ACh stimulates ion transport systems by changing the membrane permeability of the colon.
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PMID:[The effect of ATP and acetylcholine on the sodium transport in bullfrog large intestine (author's transl)]. 108 21

1 per cent Picrotoxin placed on cortex of rat caused paroxysmal ECoG discharges with concomitant increase in [Ke"] from 3 to 6.7 mM with oscillations corresponding to ictal (maximum) and interictal (minimum) spiking. Invasion of the epileptogenic focus by spreading depression was blocked when the amplitude of oscillations of [Ke+] reached 2.6 mM. Epileptogenic activity induced by topical 10 per cent pentazol caused a less marked increase in [Ke+] (4.6 mM) and did not prevent depression from invading the focal area, but did diminish [Ke+] from the normal of 60 to 70 mM to 39 mM. It is concluded that seizure-induced depolarization of neural elements in deep cortical layers, though inadequate to trigger spreading depression, does prevent it from spreading, in part by activating the sodium pump.
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PMID:Blockage of cortical spreading depression by picrotoxin foci of paroxysmal activity. 112 95

Activation of the electrogenic sodium pump by means of increasing concentration of intracellular sodium ions in identified neurons A and B of the mollusc was followed by the hyperpolarization, decrease of the excitability, and depression of the neurons rhythmic activity. Apart from that, the amplitude and the maximal rates of rise of ascending (VB) and descending (VH) phases of action potential (AP) were almost unchanged. The depression of the electrogenic sodium pump activity due to 2,4-DNP and potassium-free medium, led to the depolarization, increase of excitability and frequency of the rhythmic activity, and decrease of AP, VB, and VH. The decrease and increase of the excitability may be explained by the changes of the critical level of depolarization. The decrease of AP, VB and VH may be accounted for by the changes of time parameters of activation and inactivation of sodium and potassium channels which are characteristic for the depolarization effect.
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PMID:[Bioelectrical characteristics of the membrane of identified Coretus corneus mollusk neurons A and B upon activation and blocking of the electrogenic sodium pump]. 121 95

Evidence is presented in support of the hypothesis that transmitter monoamines can exert their post-synaptic effects by stimulation or inhibition of Na+/K(+)-ATPase in neuronal or glial cell plasma membranes. Stimulation of electrogenic sodium pumping, causing a hyperpolarization with an increase in membrane resistance, could account for the depression of neuronal spontaneous firing and the signal/noise enhancing actions of these amines. Conversely, inhibition of an electrogenic sodium pump in neuronal plasma membranes would lead to depolarization and enhanced excitability.
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PMID:Na+/K(+)-ATPase as an effector of synaptic transmission. 136 11

Current theories of the causes of somatic symptoms in depression neglect evidence for a general inhibition of Na,K-ATPase. Experimentally, sodium pump inhibition is associated with depolarization of electrically active tissue: the threshold of peripheral nerves is decreased and smooth muscle function altered. Symptoms compatible with these changes are found both in depression and intoxication with digoxin, which inhibits Na,K-ATPase. The hypothalamus contains inhibitors of Na,K-ATPase which are capable of producing depolarization. In depression, changes in hypothalamic activity may increase endogenous inhibition and contribute to the somatic symptoms.
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PMID:Disturbed hypothalamic control of Na,K-ATPase: a cause of somatic symptoms of depression. 242 32


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