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)

1. The responses of bladder strips from control, streptozotocin-diabetic, and sucrose-drinking rats to electrical field stimulation were investigated. Sucrose-drinking rats were included as additional controls because they have enlarged bladders as a result of non-diabetic diuresis. 2. Bladder strips from diabetic rats developed more spontaneous activity than those from the two control groups. Indomethacin reduced the amplitude and frequency of spontaneous contractions suggesting that they resulted from endogenous prostaglandin formation. Tetrodotoxin (TTX) had little effect, while alpha, beta-methylene ATP caused increases in spontaneous activity. 3. Bladder strips from diabetic rats responded to field stimulation with greater contractions than controls in the absence of antagonists as well as in the presence of atropine and alpha, beta-methylene ATP. Increasing TTX concentrations caused a step-wise depression of the contractile response to electrical stimulation which was not affected by preincubation with either atropine or alpha, beta-methylene ATP. 4. Atropine and indomethacin had no effect on strength-duration curves constructed to measure threshold contractile responses to five pulses stimulation. The curves were shifted to the right by both TTX and alpha, beta-methylene ATP, indicating that the responses were neurogenic in nature and at least partially, the result of stimulation of P2-purinoceptors. In the absence of drugs, bladder strips from diabetics responded at lower voltages and pulse widths than those of control and sucrose-drinking rats, suggesting that they were more excitable. 5. The response curve of bladder strips from diabetics to field stimulation at increasing voltage was shifted upwards and to the left compared to strips from control or sucrose-drinking rats. 6. Bladder strips from diabetics responded to stimulation at increasing pulse width with greater responses than those from control or sucrose-drinking rats. At 1.0 ms pulse width, the TTX-resistant response of strips from diabetic rats was still greater than that of the other groups, indicating that a myogenic component was also involved.7. The data suggest that bladder strips from diabetic rats are more excitable than those of control or sucrose-drinking rats. This may result from diabetes-induced decreases in bladder lipid or other membrane changes, and/or be a result of partial depolarization, perhaps related to diabetic neuropathy.
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PMID:Factors underlying the increased sensitivity to field stimulation of urinary bladder strips from streptozotocin-induced diabetic rats. 781 10

We tested the hypothesis that acute lung injury (ALI) isolated to a perfused in situ left lung preparation results in sustained reflex cardiovascular depression. Phorbol myristate acetate (PMA), an agent that activates neutrophils, administered into the isolated lung preparation of chloralose-anesthetized dogs resulted in ALI, as assessed by wet-to-dry weight ratios and histopathology, and significant decreases in heart rate (43%), mean arterial pressure (27%), aortic blood flow (29%) and maximum rate of change in left ventricular pressure (30%). Significant reflex effects occurred by 20 min after PMA administration and were sustained for 40 min (n = 7). Hemodynamic variables recovered when the left lung was denervated 60 min after PMA administration. Indomethacin administered into the isolated circulation before PMA (n = 5) did not significantly influence the ALI or reflex effects. Systemic atropinization (n = 6) prevented only the bradycardia. Left lung denervation before ALI (n = 3) prevented all reflex effects. We conclude that PMA administration into an isolated in situ lung preparation results in ALI and sustained reflex cardiovascular depression that is most likely elicited by pulmonary C-fiber stimulation and mediated by withdrawal of sympathetic efferent nerve activity.
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PMID:Acute lung injury isolated to an in situ lung preparation causes sustained reflex cardiovascular depression in dogs. 783 9

1. We have previously found that the P2x-purinoceptor agonist, alpha, beta-methylene adenosine 5'-triphosphate (alpha, beta-methylene ATP), depolarizes the rat cervical vagus nerve, measured with a 'grease-gap' extracellular recording technique. This effect was attenuated by the P2 purinoceptor antagonist, suramin. In the present study we have investigated in more detail the antagonism produced by suramin and have also investigated the actions of two other putative P2 purinoceptor antagonists, cibacron blue and pyridoxal-phosphate-6-azophenyl-2', 5'-disulphonic acid (iso-PPADS). Furthermore, we have studied the interactions between suramin and cibacron blue or iso-PPADS in an attempt to determine whether these antagonists act at a common receptor site. 2. Suramin (1 x 10(-5)-1 x 10(-4) M) produced reversible, concentration-related rightward displacements of the concentration-effect curve to alpha, beta-methylene ATP. Schild analysis of this antagonism yielded a pA2 value of 5.90 with a slope value of 0.47. 3. Cibacron blue (3 x 10(-5)-1 x 10(-4) M) also antagonized depolarizations induced by alpha, beta-methylene ATP. The antagonistic effects of cibacron blue were slow to reach equilibrium but could be readily reversed on washout. At low concentrations for antagonism, cibacron blue (1 x 10(-5) M and 3 x 10(-5) M) produced enhancement of the maximal response to alpha, beta-methylene ATP. At the highest concentration tested (1 x 10(-4) M) the concentration-effect curve to alpha, beta-methylene ATP was shifted to the right in a parallel manner, yielding a pKB estimate of 4.96. 4. Iso-PPADS (1 X 10-6 1 X 10-5- M) produced a concentration-related depression in the maxima ofthe concentration-effect curves to alpha,beta-methylene ATP. Analysis of these data by a double reciprocal plot yielded a pKB estimate of 6.02. This profile of insurmountable antagonism could not be attributed to irreversible binding of iso-PPADS to the receptor since the effect of iso-PPADS could be reversed on washing, albeit slowly.5. In the presence of suramin (1 x 10-4 M), cibacron blue (1 x 10-4 M) produced no further rightward displacement of the alpha,beta-methylene ATP concentration-effect curve. The mean agonist concentration ratios in the presence of suramin or cibacron blue alone (11.7 and 10.3, respectively) were not significantly different from the mean concentration-ratio in the presence of both antagonists (11.8). This finding suggests that high concentrations of alpha,beta-methylene ATP activate a receptor population which is resistant to blockade by either antagonist.6. The antagonistic effect of iso-PPADS (1 x 10-5 M) was partially attenuated by suramin (1I x 10-4 M).It is possible that this interaction reflects a slow dissociation of iso-PPADS from the receptor with which suramin and alpha,beta-methylene ATP interact.7. Suramin, cibacron blue or iso-PPADS had no marked effect on depolarization produced by 5-hydroxytryptamine (5-HT, 1 x 10-7-3 x 10-5 M), indicating their specificity in antagonizing responses to alpha, beta-methylene ATP.8. Responses to alpha,beta-methylene ATP were not antagonized by 8-para-sulphophenyltheophylline (3 x 10-5M), ondansetron (1 x 10-7 M), bicuculline (1 x I0-5 M), phentolamine (1 X 10-6 M) or hexamethonium(1 X 10-4 M), which are antagonists at P1-purinoceptors, 5-HT3 receptors, GABAA receptors, a-adrenoceptors and nicotinic cholinoceptors, respectively, thereby excluding the involvement of these receptors.Indomethacin (3 X 10-6 M) had no effect on responses to alpha,beta-methylene ATP.9. The results obtained with three purinoceptor antagonists confirm and extend our original supposition that alpha,beta-methylene ATP-induced depolarization of the rat vagus nerve is mediated predominantly via P2 purinoceptors, thought to be of the P2,X subtype. The finding that responses induced by high concentrations of agonist were resistant to blockade by suramin and cibacron blue, but could be attenuated by iso-PPADS, adds further weight to our speculation that the purinoceptor population in the rat vagus nerve is heterogeneous.
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PMID:The use of antagonists to characterize the receptors mediating depolarization of the rat isolated vagus nerve by alpha, beta-methylene adenosine 5'-triphosphate. 803 52

Elucidation of the mechanisms of placental dysfunction after bypass and the negative effects of fetal stress (Fig 9) has allowed these issues to be addressed effectively using indomethacin and appropriate fetal anesthesia. The effective management of these two major problems has made a dramatic difference in the ability of fetal animals to survive surgical intervention and extracorporeal circulation. Characterization of various aspects of placental vascular hemodynamics using the isolated placental preparation also has added new insights into the behavior of the placental vasculature during extracorporeal circulation. These insights have been and will continue to be extremely useful in designing the ideal method of fetal extracorporeal circulatory support. In spite of these advances, further work remains before clinical application of these techniques can be applied reliably. Ideally, a specific blocker of the mediators of the placental response to cardiac bypass should be available before clinical studies are undertaken. Indomethacin, although quite effective, may have secondary effects on other vascular beds that would be potentially detrimental. Also, although the fetal stress response can be blocked adequately using fetal total spinal anesthesia, with a dramatic improvement in cardiovascular stability, this technique of anesthesia not only would be cumbersome, but also would be potentially dangerous in the human fetus. High-dose narcotic anesthesia has been shown to be very effective in neonates and infants undergoing cardiac procedures, with respect to both blockage of the stress response and maintenance of cardiac function. This technique also may be applicable in the human fetus as an effective method of blocking the stress response without causing myocardial depression or affecting peripheral vascular resistances. Unfortunately, sheep do not possess opiate receptors and, therefore, are not an appropriate model for testing narcotic anesthesia in the fetus. Future studies in the primate model using high-dose narcotic anesthesia could provide important information regarding this problem. Also, the ideal circuitry for fetal extracorporeal support has not been determined with certainty. Although a simplified circuit without an oxygenator is possible if the placenta is used as the oxygenator, this method has the disadvantages of high flow rates and placental stimulation. Extracorporeal circulation with the inclusion of an artificial oxygenator requires a somewhat more complex circuit; however, more manageable flow rates and less stimulation of placental vasculature are possible with this technique (Fig 10). All forms of fetal intervention for cardiovascular disease require an extensive understanding of the fetal pathophysiologic responses to intervention, whether the intervention involves open techniques that necessitate extracorporeal circulatory support or closed interventional techniques.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Fetal cardiac surgery. 811 96

Angiotensin II (AII) receptors in guinea pig isolated esophageal muscularis mucosae (EMM), stomach fundus, gall bladder, ileum, colon and thoracic aorta have been characterized by peptide agonists and nonpeptide antagonists in the presence of peptidase inhibitors. Angiotensin peptides contracted every preparation studied; the potency order typically was [Sar1]AII > or = AII > angiotensin III (AIII) > or = [Val4]AIII >> AI >>> [des Phe8]AII. AI was ineffective everywhere except the gall bladder, where it acted as a full agonist. Tetrodotoxin (1 microM) and atropine (1 microM) did not affect the AII response in EMM, fundus and gall bladder. In ileum, AII and AIII were equieffective, and both the maximal response and potency were decreased by tetrodotoxin and atropine. Indomethacin (3 microM) abolished response to AII in the fundus but had little effect on the gall bladder and the atropine-resistant component of the ileal response. The AT1-selective antagonist losartan (DuP 753) antagonized responses to AII in all tissues with similar affinities when there was no depression of maximal response (pKB = approximately 8-8.3). The AT2-selective antagonist PD123177 (10 microM) failed to antagonize responses to AII in any tissue. These data suggest the presence of AT1 receptors in intestinal and vascular smooth muscles of the guinea pig. It is unclear whether all AT1 receptors are similar because of the differential potency order observed in the presence of peptidase inhibitors. Of the isolated tissue investigated, responses to AII are robust and reproducible in the ileum, fundus and gall bladder.
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PMID:Characterization of angiotensin II receptors in smooth muscle preparations of the guinea pig in vitro. 826 14

Tooth drift requires the deformation of the root socket and the adjustment of the other components of the attachment apparatus, namely, the periodontal ligament (PDL) and the cementum. Indomethacin (7.5 mg/kg/d), an inhibitor of prostanoid synthesis, provoked in rats a depression in the bone resorption effecting the deformation of the socket (Lasfargues and Saffar, Anat. Rec., 234:310-316, 1992). In the present paper we examined the consequence of this treatment both on the PDL and the root surface. After 3 days of treatment, when osteoclastic resorption was not yet disturbed, the root had been markedly resorbed (P < 0.05) opposite the resorbing bone surface; at that time the PDL width remained in the normal range. After 7 days, i.e., when the bone resorption was depressed, the PDL was widened as the result of the ongoing root resorption. Despite the extensive root resorption, the anchorage of the PDL fibers appeared to remain effective, suggesting that it was rapidly restored. On day 14 at the time of the bone resorption recovery, cementum was deposited in the root resorption lacunae and the PDL width had returned to its control value. As early as day 3 the daily rate of dentine formation increased in the pulp area subjacent to the root resorption lacunae (P < 0.01). These data demonstrate that i) the responses of the different components of the periodontal apparatus are coordinated to allow for the maintainance of the PDL width so that when bone resorption is disturbed, root resorption compensates for it, and ii) the odontoclasts can differentiate and resorb under prostanoid inhibition whilst osteoclastic resorption of the bone socket is inhibited.
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PMID:Inhibition of prostanoid synthesis depresses alveolar bone resorption but enhances root resorption in the rat. 831 Dec 58

Cirrhotic rats have an increased susceptibility to ethanol-induced gastric injury, related to an inability to mount a defensive gastric hyperemic response to luminal irritants, and associated with an impaired reactivity of the gastric microcirculation to nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)-dependent vasodilators. Whether this hyporesponsiveness is in some way related to depressed prostaglandin synthesis by the stomach of cirrhotic rats is not clear. The aims of this study were to evaluate the role of NO and prostaglandins in the regulation of the gastric microcirculation under resting conditions and in response to administration of sodium nitroprusside, as well as to investigate the mechanisms of the hyporesponsiveness of the gastric microcirculation to nitrovasodilators. Cirrhosis was induced in rats by bile duct ligation, and controls had sham-operation. NG-nitro-L-arginine-methyl-ester (L-NAME) and indomethacin administration produced a greater reduction in gastric blood flow in cirrhotic rats than controls. Indomethacin pretreatment almost completely abolished the responsiveness to sodium nitroprusside (NaNP) in cirrhotic rats, while not affecting controls. Long-term administration of misoprostol to cirrhotic rats restored to normal the responsiveness to NaNP, whereas long-term administration of aspirin to healthy rats resulted in a hyporesponsiveness of the gastric microcirculation to NaNP similar to that seen in cirrhotic rats. We conclude that there are interactions between NO and prostaglandins in regulating gastric blood flow in both healthy and cirrhotic rats. The hyporesponsiveness of the gastric microcirculation of cirrhotic rats to a nitrovasodilator may occur as a consequence of prolonged depression of gastric prostaglandin synthesis.
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PMID:Prostaglandins modulate the responsiveness of the gastric microcirculation of sodium nitroprusside in cirrhotic rats. 855 31

We have studied the duration of the ACTH inhibition effect on the incorporation and transformation of [1-14 C] eicosatrienoic acid, in isolated adrenocortical cells of normal rats. The effect of esculetin, indomethacin and nordihydroguaiaretic acid alone, or in the presence of ACTH or diBucAMP on arachidonate biosynthesis was also investigated. ACTH and diBucAMP produced a significant inhibition in arachidonic acid biosynthesis. The inhibition produced by ACTH on delta 5 desaturating activity was considered to be a short-term effect. Nordihydroguaiaretic acid and esculetin provoked a depression in the uptake of 20:3 (n-6) acid and an inhibition in the formation of 20:4 (n-6) acid by adrenocortical cells. This effect was potentiated when the cells were currently treated with either ACTH or diBucAMP. Indomethacin produced no changes in the uptake of 20:3 (n-6) acid, while induced an increment on delta 5 desaturation activity. This effect would indicate that, normally, the metabolites produced by the cyclooxygenase pathway would operate by depressing arachidonic acid biosynthesis. Considering the negative regulation of the delta 5 desaturase activity system produced by ACTH through cAMP, and the positive modulation inferred by the results obtained in this work, it is possible to assume that there are, at least, two mechanisms that take place on 20:4 (n-6) acid formation. These mechanisms seem to work independently from one another and they probably interact when effecting a bi-directional control.
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PMID:Indomethacin, esculetin and nordihydroguaiaretic acid modify arachidonate biosynthesis in rat adrenocortical cells. 858 May 30

Microglia and astrocytes are transformed into reactive glia (RG) by brain disease and normal function. Eicosanoids and nitric oxide (NO), two intercellular mediators, may influence gliosis. We investigated how drugs that alter production of these paracrine signals effect induction of glial reactivity from spreading depression. Unilateral (left) neocortical spreading depression was induced in 95 halothane anesthetized rats by intracortical injections of 0.5 M KCl, with or without drug treatment (five animals/group). Immunohistochemical staining (IS) intensity using the OX-42 and anti-glial fibrillary acidic protein (GFAP) antibodies determined reactivity in microglia and astrocytes, respectively. After 3 days, brains were processed for OX-42 and GFAP-IS and mean optical densities (OD) of IS were measured. Average OD's (for OX-42) and the log ratio (left/right) of OD's (OX-42 and GFAP) were compared to normal animals. Spreading depression induced significant log ratios for both OX-42- and GFAP-IS (P's < 0.01). However, dexamethasone (a glucocorticoid), nordihydroguaiaretic acid (a lipoxygenase inhibitor), and nitroprusside (a NO donor) prevented significant left sided and log ratio OD values for microglia (P's > 0.05). L-Name, a NO synthase inhibitor, caused significant increases in left and right OD's for microglia (P's < 0.05). Mepacrine, a phospholipase A2 inhibitor, Indomethacin, a cyclooxygenase inhibitor, and phenylephrine, an adrenergic agonist, did not prevent induction of significant OX-42 log ratios (P's < 0.01, 0.05, 0.01), and resulted in increases in left side OD's (P's < 0.01, 0.05, 0.05). Significant GFAP log ratios occurred after spreading depression in all drug groups, P's < 0.01. Thus, induction of reactivity in microglia is more sensitive to eicosanoids and NO than in astrocytes.
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PMID:Eicosanoids and nitric oxide influence induction of reactive gliosis from spreading depression in microglia but not astrocytes. 872 5

The actions of the nonsteroidal antiinflammatory drug niflumic acid were studied on frog neuromuscular preparations by conventional electrophysiological techniques. Niflumic acid reduced the amplitude and increased the latency of endplate potentials in a concentration-dependent manner. Neuromuscular junctions pretreated with niflumic acid (0.05-0.5 mM) showed much less depression than control when they were stimulated with trains of impulses. Inhibition of acetylcholine release was reverted by raising the extracellular Ca(2+) concentration but not by simply washing out the preparations with niflumic acid-free solutions. Pretreatment with indomethacin (0.1 mM), another nonsteroidal antiinflammatory drug, did not affect the niflumic acid-induced inhibition of evoked responses. Niflumic acid (0.1 mM) did not change the amplitude of miniature endplate potentials and had a dual action on the frequency of miniatures: it decreased their frequency at 0.1 mM whereas it produced an enormous increase in the rate of spontaneous discharge at 0.5 mM. Niflumic acid (0.1 - 1 mM) reversibly increased the amplitude and affected the kinetics of presynaptic voltage-activated K+ current and Ca(2+)-activated K(+) current in a concentration-dependent manner. Niflumic acid (0.1 - 1 mM) irreversibly decreased the amplitude and reversibly affected the kinetics of the nodal Na(+) current. Indomethacin (0.1 mM) had no effect on presynaptic currents. In conclusion, niflumic acid reduces acetylcholine release by increasing presynaptic K+ currents. This may shorten the depolarizing phase of the presynaptic action potential and may reduce the entry of Ca(2+) with each impulse.
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PMID:Niflumic acid-induced increase in potassium currents in frog motor nerve terminals: effects on transmitter release. 886 25


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