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 general pharmacology of aclacinomycin A, a new antitumor antibiotic, was studied in mice, rats, guinea-pigs, frogs, rabbits and dogs. The LD50 values of aclacinomycin A were 32.5 mg/kg (i.v.), 30.1 mg/kg (i.p.), 33.9 mg/kg (s.c.) and 69.7 mg/kg (p.o.), respectively in male mice, and 28.8 mg/kg (i.v.), 21.1 mg/kg (i.p.), 26.4 mg/kg (s.c.) and 58.6 mg/kg (p.o.), respectively in male rats. Aclacinomycin A had no effect on the central nervous system except potenciation of the pentobarbital sodium-induced anesthesia in mice. The contraction of isolated heart was stimulated in frogs while slightly inhibited in rabbits at higher concentration. Transient increases in the heart rate and the blood flow of peripheral vasculature were observed but the blood pressure was slightly lowered with respiratory excitation in anesthetized rabbits and dogs. The ECG (II-lead) demonstrated slight depression of R wave amplitude and slight sinus arrhythmia in dogs. Aclacinomycin A inhibited the contraction of isolated smooth muscle and antagonized some spasmogens. It inhibited the spontaneous movement of isolated rabbit ileum and rat uterus at higher concentration, and antagonized acetylcholine, histamine, serotonin and barium chloride in the contraction of isolated guinea-pig ileum. The antagonism was competitive to oxytocin and noncompetitive to acetylcholine in rat uterus, and noncompetitive to noradrenaline in rat deferent duct. The drug showed no apparent effect on the gastrointestinal propulsion in mice and on mucous membrane of the stomach in rats. However, it depressed gastric acid secretion in rats while slightly increased bile secretion in guinea-pigs. Urine volume and urinary excretion of electrolytes (Na+, K+) decreased in rats. Vascular permeability was slightly inhibited by the drug in rabbits and mice. No hemolytic effect was shown. Aclacinomycin A showed no antigenicity in anaphylactic reaction and SCHULTZ-DALE reaction in guinea-pigs.
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PMID:[General pharmacology of aclacinomycin A (author's transl)]. 692 61

The contraction of the potassium depolarized pulmonary artery of the guinea pig was diminished by the calcium antagonists nifedipine, gallopamil, diltiazem, verapamil and prenylamine. The drugs are listed here in order of activity. The uptake of 45Ca of the depolarized pulmonary artery was reduced by nifedipine, verapamil and prenylamine in this order of activity. The depression of the coronary flow of the isolated guinea pig heart, which was brought about by barium chloride, antigenic rabbit serum or vasopressin plus oxytocin was reduced by infusion of prenylamine. The positive inotropic effect of K-strophanthin on the isolated, electrically stimulated left atrium of the guinea pig heart was reduced by gallopamil, verapamil, prenylamine, diltiazem and nifedipine in this order of activity.
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PMID:Effects of calcium antagonists on coronary spasm and pulmonary artery contraction in comparison to their antagonistic action against K-strophanthin in isolated guinea pig atria. 710 Feb 59

1. alpha 1-Adrenoceptor activation caused two separate effects in rat dorsal raphe neurons: a depolarization and an increase in the duration of the after-hyperpolarization following the action potential. The depolarization often resulted in repetitive action potentials. The alpha 1-adrenoceptor antagonists prazosin and WB 4101 blocked the depolarization induced by phenylephrine. The concentration-response curve to phenylephrine was shifted to the right by WB 4101. 2. Under voltage clamp, alpha 1-adrenoceptor agonists caused an inward current at -60 mV, which often became smaller at negative potentials but rarely reversed polarity even at strongly negative potentials. Using whole-cell recording, the inward current reversed polarity at the equilibrium potential for potassium in the majority of cells. Intracellular Cs+ decreased or abolished the alpha 1-mediated inward current. The inward current was dependent on external calcium, but not on the degree of internal calcium buffering. Removal of external calcium or addition of MgCl2, CoCl2 or CdCl2 reduced or blocked the effects of alpha 1-adrenoceptor agonists. Barium and strontium supported and even augmented the inward current induced by alpha 1-adrenoceptor agonists, whereas nifedipine and omega-conous toxin had no effect. In contrast, internal dialysis with the calcium chelator 1,2-bis(O-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid (BAPTA) did not inhibit the inward current. 3. The alpha 1-induced depolarization was blocked (or occluded) by the inclusion of GTP-gamma-S (100 microM) in the recording pipette. The phorbol-ester 4-phorbol 12,13-dibutyrate (PDBu) had no action on the membrane potential and depressed the phenylephrine-induced depolarization. This depression was reversed by the non-selective protein kinase inhibitor staurosporin. 4. Phenylephrine and noradrenaline increased a late component of the after-hyperpolarization (late-AHP) that followed a single action potential. The alpha 1-sensitive late-AHP was blocked by apamine suggesting that it is a calcium-dependent potassium conductance. 5. Thapsigargin reduced the duration of the late-AHP and blocked the phenylephrine-mediated prolongation. Caffeine also augmented the late-AHP and ryanodine blocked the augmentation induced by caffeine. The augmentation induced by phenylephrine was not occluded by caffeine and was still present after the caffeine-induced augmentation was blocked by ryanodine. 6. In slices pretreated with manoalide the depolarization induced by alpha 1-agonists was not changed; however, the late-AHP was reduced in duration and the alpha 1-receptor-mediated augmentation of the late-AHP was decreased.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Alpha 1-adrenoceptors in rat dorsal raphe neurons: regulation of two potassium conductances. 752 47

One hundred dogs (83 intact males, 15 castrated males, and two intact females) underwent 110 perineal herniorrhaphy procedures. Mixed-breed dogs (n = 32), miniature poodles (n = 14), Boston terriers (n = 11), and Pekingese (n = 9) were represented most frequently. Perineal swelling (n = 48) and a perineal defect on rectal palpation (n = 31) were common clinical signs. Twenty dogs had urinary bladder retroflexion and were significantly more likely to have elevated serum urea nitrogen and creatinine concentrations, hyperkalemia, hyperphosphatemia, and neutrophilic leukocytosis. Only five of 43 dogs evaluated radiographically had prostatomegaly. Of 30 dogs receiving oral barium, all had rectal deviation. The most frequent complications during the hospitalization period were incisional (n = 35), followed by rectal prolapse (n = 9), tenesmus (n = 8), and depression (n = 8). Fifty-six of 70 dogs with follow-up had no complications.
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PMID:Perineal herniorrhaphy: perioperative data from 100 dogs. 755 67

Unless renal function is impaired or rhabdomyolysis is severe, hyperkalemia is a relatively uncommon metabolic complication of poisoning. In contrast, marked hypokalemia is a more common problem and may have serious sequelae. Most potassium disturbances in acute poisoning are due to disruption of extra-renal control mechanisms, notably the activity of Na+/K+ ATPase and K+ channels. Hypokalemia occurs because of increased Na+/K+ ATPase activity (e.g. beta 2 agonist, theophylline or insulin poisoning), competitive blockade of K+ channels (e.g. barium or chloroquine poisoning), gastrointestinal losses and/or alkalosis. Hyperkalemia follows inhibition of Na+/K+ ATPase activity (e.g. by digoxin), increased uptake of potassium salts, disruption of intermediary metabolism (e.g. cyanide poisoning), activation of K+ channels (e.g. fluoride poisoning), and the presence of acidosis and rhabdomyolysis, particularly if the latter is complicated by renal failure. Hypokalemia results in generalized muscle weakness, paralytic ileus, ECG changes (flat or inverted T waves, prominent U waves, ST segment depression) and cardiac arrhythmias (atrial tachycardia +/- block, AV dissociation, VT, VF). Hyperkalemia is associated with abdominal pain, diarrhea, muscle pain and weakness, ECG changes (tall peaked T waves, ST segment depression, prolonged PR interval, QRS prolongation) and cardiac arrhythmias (VT, VF). Significant disturbances of potassium homeostasis are often unrecognized and may cause considerable morbidity and mortality. Prompt recognition and appropriate treatment of these disturbances could be life-saving.
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PMID:Disturbances of potassium homeostasis in poisoning. 762 96

The association of potassium ions with the occurrence and propagation of spreading depression is well known. The effects of barium ions, a potassium-channel blocker, on spreading depression in isolated retina are described. Pulses of 1-4 mM BaCl2, when applied to the retina, first induce the reaction, then hinder the propagation of the wave which finally stops. The threshold level which triggers the reaction is 0.4-0.6 mM BaCl2 but it varies with the composition of the superfusing Ringer solution. For example, in retinas superfused with low NaCl, or NaCl partially substituted by sodium isethionate, spreading depression may be evoked by barium ions at micromolar concentrations, without changing the velocity of spreading. The delayed blocking actions observed with higher doses may predominantly affect the recovery processes of the wave front, and are related to the refractory period of a preceding spreading depression.
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PMID:Elicitation of retinal spreading depression by barium ions. 764 Jun 38

To estimate the smallest unit of mucosa in the duodenal bulb radiologically, double contrast radiographs were investigated in correlation with endoscopy and histological examinations of biopsy specimens. Fine mucosal structures in the duodenal bulb were observed in 692 out of 1463 cases (47.4%) in double contrast radiographs in our upper gastrointestinal series from January, 1989 to December, 1990. Fine mucosal structures were subdivided into 3 categories: A; reticular and/or granular pattern (60.1%, 416/692), B; diffuse nodular pattern with or without additional A pattern (35.3%, 244/692), and C; diffuse tiny barium dots (4.6%, 32/692). Three pattern groups were reviewed by endoscopic and histological assessment of biopsy specimens in comparison with the control group of nonvisualized mucosal pattern (30 cases). Endoscopic observation was carried out in 170 out of 692 radiology cases in respect to irregularities in the duodenal mucosa (villous pattern, mucosal colour, nodule or depression, or disease) and associated diseases of the stomach. Fewer diseases (1 ulcer scar and 7 cases of the duodenitis, 15.6%) were visualized in the duodenal bulb than the stomach due to a prominent acid secretive function, which was confirmed by the Congo-Red method in groups A and B. A flat villi pattern was noted with accompanying disease in the duodenal bulb in 8 out of 11 cases of in group C (72.7%). By the Whitehead classification of duodenitis, 100% of group A, 98.5% of group B and 100% of group C revealed low grade inflammation (Grade < 2) in histological examinations of biopsy specimens (120 cases). The nodule seen in B pattern was histologically composed of nonspecific protruded mucosa (38%, 19/50), proliferation of lymphoid follicle (36%, 18/50), Brunner's gland hyperplasia (24%, 12/50) or heterotopic gastric mucosa (2%, 1/50). Consequently, mucosal patterns A, B and part of C might be appropriate as basic mucosal units of the normal duodenal bulb in double contrast radiograph.
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PMID:[A study on the fine mucosal pattern in the duodenal bulb]. 780 17

The retina is the most accessible piece of central gray matter in the vertebrate brain. Its wide dynamic operational range makes it the ideal neuronal network to study its excitability. Spreading depression waves in the retina are accompanied by strong intrinsic optical signals (IOS) and thus can be measured non-invasively with optical methods. Additionally, incubation with fluorescent dyes allows to follow calcium fluxes in parallel. The IOS can be divided into red and green scatter of light. We show that during spreading depression the red scatter signal precedes the green scatter signal and that the calcium signal matches the red scatter signal. Incubation of the retina with barium chloride leads to a reversible depression of red scatter and calcium signal whereas the green scatter signal is hardly effected. The wave propagation velocity is reduced, too. This supports the idea that the early red scatter signal is a direct visualisation of glial membrane potential and that glia cells in the chicken retina are involved in the control of extracellular calcium.
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PMID:Calcium waves in gray matter are due to voltage-sensitive glial membrane channels. 785 Apr 73

1. Whole cell voltage-clamp techniques were used in the CA1 region of rat hippocampal slices to study presynaptic and postsynaptic gamma-aminobutyric acid B (GABAB) response mechanisms. The effects of the protein kinase C activator phorbol 12,13-diacetate (PDA), barium (Ba2+), and pertussis toxin were compared on the presynaptic and postsynaptic GABAB actions of bath-applied baclofen and paired-pulse depression (PPD) of the monosynaptic GABAA inhibitory postsynaptic current (IPSC). The magnitude of PPD was dependent on the amplitude of the first response. PPD was predominantly a GABAB-mediated effect, as it was very much reduced by the GABAB antagonist CGP 35348. 2. PDA enhanced monosynaptic GABAA IPSCs through an apparently presynaptic mechanism. Iontophoretic GABAA responses were unaffected, and there was no change in EIPSC. PDA increased the frequency of spontaneous, tetrodotoxin-insensitive IPSCs without significantly affecting their amplitudes. The inactive phorbol ester, 4 alpha-PDA did not alter IPSCs. After PDA application, stimulus intensity was adjusted to produce responses of comparable amplitude to control responses. PDA had a marked and reversible depressant effect on the postsynaptic GABAB response and caused a lesser, but still significant, reduction in the baclofen-induced reduction of monosynaptic IPSCs. PDA had no effect on PPD. 3. Ba2+ dramatically reduced postsynaptic GABAB responses; it had no effect on PPD. Ba2+ tended to decrease the presynaptic baclofen reduction of IPSCs, although this was not statistically significant. 4. Pertussis toxin, injected 2-3 days earlier into the intact hippocampus, blocked all three GABAB responses equally (approximately 70% decrease). 5. We conclude that presynaptic and postsynaptic GABAB mechanisms are mediated by G proteins that couple to different mechanisms. Discrepancies with previous work are evidently due to the use of different tissue preparations and different target responses. Even though protein kinase C activation caused a partial reduction in the presynaptic effect of baclofen, its lack of effect on PPD makes a significant role for protein kinase C in modulation of PPD unlikely.
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PMID:Differences between presynaptic and postsynaptic GABAB mechanisms in rat hippocampal pyramidal cells. 788 61

1. The kinetics and sensitivity of the Ca(2+)-dependent inactivation of calcium current (ICa) were examined in intact cell bodies from the abdominal ganglion of Aplysia californica under two-electrode voltage clamp. 2. Rapid changes in the level of intracellular free calcium ([Ca2+]i) were generated at the cell surface by photolytic release of Ca2+ (nitr-5 and dimethoxy nitrophen) or Ca2+ buffer (diazo-4). 3. Diazo-4 increased ICa by 10-15% and slowed the rate of ICa decay when photolysed before a test pulse or between a prepulse and a test pulse. The predominant effect of further light flashes was to increase the amount of non-inactivating current (I infinity) remaining at the end of long (> 1 s) depolarizing pulses. 4. A rapid increase in [Ca2+]i buffering during ICa inactivation did not cause a rapid recovery of current but merely reduced the rate and extent of subsequent inactivation. This effect was not seen when Ba2+ was the charge carrier. 5. Photolytic release of Ca2+ from nitr-5 produced estimated Ca2+ jumps of 3-4 microM at the front surface of the cell but failed to augment inactivation either before or during ICa. In contrast, photolysis of DM-nitrophen 10-90 ms before the test pulse decreased peak ICa by about 30%. A flash given during ICa rapidly blocked 41 +/- 3% of peak current with a time constant of 3-4 ms at 17 degrees C. Similar results were seen with the barium current (IBa). 6. Microinjection of the potent phosphatase inhibitor microcystin-LR (5 microM) had variable effects on ICa inactivation and augmented the cyclic AMP-induced depression of the delayed rectifier (IK(V) by forskolin (100 microM) and 3-isobutyl-1-methylxanthine (IBMX; 200 microM). 7. Full recovery from inactivation measured in two-pulse experiments took at least 20 s. This slow recovery process was unaffected by increases in intracellular cyclic AMP elicited by direct injection or by bath application of forskolin and IBMX. It was also unaffected by decreases in cyclic AMP induced by injecting 2',5'-dideoxyadenosine (1 mM) or bath application of the Rp isomer of cyclic adenosine 3',5'-monophosphothioate (Rp-cAMPS; 200 microM). 8. A 'shell' model relating submembrane Ca2+ to inactivation was inconsistent with the experimental results since it greatly overestimated the effects of diazo-4 and predicted significant inactivation by nitr-5 photolysis. 9. A model linearly relating [Ca2+]i in a single Ca2+ channel 'domain' to inactivation more closely matched the experimental results with diazo-4 and DM-(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ca(2+)-dependent inactivation of Ca2+ current in Aplysia neurons: kinetic studies using photolabile Ca2+ chelators. 822 15


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