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. Effects of PAF on excitatory neuro-effector transmission in smooth muscle cells of mucosa-free trachea and epithelium-intact bronchiole of the dog were investigated, by isometric tension recording, microelectrode and double sucrose-gap methods. 2. PAF (10(-11)-10(-7) M) dose-dependently enhanced the amplitude of contraction evoked by repetitive field stimulations (10 stimuli at 20 Hz) in both tracheal and bronchiolar tissues. At higher concentrations PAF (> 10(-8) M) increased the amplitude of contraction to a greater extent in the bronchiole than in the trachea. 3. In both muscle tissues, in parallel to the amplitude of contraction, PAF markedly enhanced the amplitude of excitatory junction potentials (e.j.ps) evoked by a single field stimulation in a dose-dependent manner, with no change in the resting membrane potential or input membrane resistance of the smooth muscle cells. PAF (5 x 10(-7) M) enhanced the amplitude of e.j.p. to a greater extent in the bronchiole than in the trachealis. In contrast, lyso-PAF (10(-10)-10(-7) M) showed no effect on e.j.p. amplitude in bronchiolar tissues. At a high concentration (10(-7) M) lyso-PAF slightly enhanced the e.j.p. amplitude in tracheal tissue, however the lyso-PAF induced stimulation of e.j.p. amplitude in the trachea was small compared to that of PAF. 4. PAF (10(-7) M) had no effect on the membrane depolarization induced by acetylcholine (ACh, 10(-9)-10(-5) M) and carbachol (10(-9)-10(-5) M) in tracheal smooth muscle cells. 5. The PAF-antagonists CV3988 (5 x i0-7 M) or WEB2086 (5 x 10-7 M) significantly enhanced the e.j.p. amplitude themselves, PAF (5 x 10-8 M) further enhanced the ej.p. amplitude in the presence of WEB2086 (5 x l0-7 M) but not CV3988 (5 x 10-7 M). In contrast, the new PAF-antagonist, E 6123(5 x l0-8 M), did not affect the ej.p. amplitude itself, and completely inhibited the increase in ej.p. amplitude caused by 5 x 10-8 M PAF. On the other hand, in the presence of the Hi-antagonist,mepyramine, PAF (5 X 10-8 M) further enhanced the ej.p. amplitude.6. The leukotriene synthesis inhibitor AA-861 (10-6 M) or leukotriene antagonist ONO1078 (10-7 M)inhibited the increase in ej.p. amplitude caused by 5 X 10-8 M PAF, respectively.7. In the presence of AA-861 (10-6 M), leukotriene B4 (LTB4, 10-' M) or LTD4 (10-8 M) slightly, and LTC4 (10- M) markedly enhanced the ej.p. amplitude. In contrast, LTE4 (10-8 M) significantly suppressed the e.j.p. amplitude.8. PAF (5 x 10-8 M) attenuated the depression phenomena of ej.ps observed during double stimulus experiments at different time intervals (5-10 s), but had no effect on the summation of ej.ps during repetitive field stimulation at a high frequency (20 Hz) in the trachealis.9. These results indicate that PAF potentiates excitatory neuro-effector transmission mainly through stimulating the release of lipoxygenase products, mainly LTC4 in the dog airway smooth muscle tissues.
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PMID:Effects of PAF on excitatory neuro-effector transmission in dog airways. 133 55

Opioid peptides share the spasmogenic action of acutely administered morphine on the sphincter of Oddi. In this study, gallbladder function was assessed following chronic opioid administration. Implantation of morphine pellets (400 mg) in male guinea pigs depressed cholecystokinin-octapeptide(CCK)-induced emptying of gallbladder bile (monitored via a duodenal cannula). Gallbladder muscle strips, isolated from the morphine treated animals, showed depressed contractile responses to CCK. This antagonism was non-specific and indirectly mediated, as ACh contractions were also depressed, whereas CCK-induced contractions of gallbladder strips from untreated animals were unaffected by direct exposure to morphine (3 x 10(-6)M). The depression of CCK stimulation of bile flow by chronic morphine administration in male guinea pigs suggests that chronic exposure to opioids can impede gallbladder emptying.
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PMID:Effects of chronic morphine on biliary tract responses to cholecystokinin-octapeptide in male guinea pigs. 164 Jul 99

1. Acetylcholine (ACh), 7.5 x 10(-5) M, and carbachol, 5 x 10(-6) M (CCh) depressed the frequency of miniature endplate potentials (m.e.p.ps) in the frog (Rana temporaria) sartorius neuromuscular junction with active acetylcholinesterase to about 50-55% of the controls. 2. A similar depression was produced by the nicotinic agonists, nicotine, suberyldicholine and tetramethylammonium. 3. The muscarinic agonists, oxotremorine, methylfurmethide and methacholine were without effect on m.e.p.p. frequency. The muscarinic antagonist, atropine and the nicotinic antagonist, (+)-tubocurarine, had no effect on the depression of m.e.p.p. frequency evoked by CCh. 4. The ganglionic blockers, benzhexonium and IEM-1119, were also without effect on the CCh-evoked depression of m.e.p.p. frequency. 5. Pretreatment of muscles with anticholinesterases did not prevent the CCh-induced drop in m.e.p.p. frequency. 6. The effect of CCh was proportionally the same as in the controls in preparations where the m.e.p.p. frequency was changed by elevation of K+ and in the presence of theophylline, noradrenaline, dibutyryl adenosine 3':5'-cyclic monophosphate (db cyclic AMP) and db cyclic GMP. 7. An inhibitor of Na+,K(+)-ATPase, ouabain, 5 x 10(-5) mol l-1, prevented or reversed the depression of m.e.p.p. frequency by CCh. However, the depression was present in a nominally K(+)-free medium. Insulin and adrenaline, which are considered to be Na+,K(+)-ATPase activators, were without effect on depression of m.e.p.p. frequency. 8. The depression of m.e.p.p. frequency by 5 x 10(-6) M CCh was the same at temperatures between 5 and 30 degrees C with a Q10 near to 1.0. When threshold amounts of CCh were used (6 x 10-7 and 3 x 10-7 M), the depression was less at higher temperatures.9. The receptive structures responsible for the CCh (or ACh)-evoked depression of m.e.p.p. frequency differ pharmacologically from muscarinic, nicotinic ganglionic and neuromuscular junction ACh-receptors as well as from the synaptic cholinesterase, in contrast to previous reports (Duncan & Publicover, 1979).The low temperature-dependence points to the possibility that physical rather than biochemical processes are limiting in this presynaptic effect of cholinomimetics.
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PMID:Depression of miniature endplate potential frequency by acetylcholine and its analogues in frog. 166 83

1. The intracellular mechanism of heterosynaptic facilitation (HSF) formation in identified neurons from the snail Planorbis corneus has been studied. 2. Facilitation of excitatory postsynaptic currents (EPSC) were induced by (a) stimulation of pallial nerve, and (b) addition to extracellular saline of serotonin, NaF, papaverine, theophylline, caffeine or dibutril-cAMP. 3. A depression of EPSC in solutions containing tolbutamide, a cAMP-dependent protein kinase inhibitor was observed. 4. In some cases the similar facilitation or depression of the current induced by acetylcholine application (ACh-current) was found in the same neuron. 5. The effects on ACh-current were distorted in solutions containing caffeine, a well-known activator of calcium ions release from the intracellular depot. 6. According to our findings, we suggest that adenylate cyclase activity of postsynaptic cells could underlie the formation of HSF and it is likely that this activity was modulated by intracellular concentration of calcium ions.
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PMID:Analysis of heterosynaptic facilitation in identified giant neurons from cerebral ganglion of the pond snail Planorbis corneus. 167 48

The effects of low concentrations (nanomolar) of d-tubocurarine (TC) on end-plate potential (EPP) and miniature end-plate potential (MEPP) amplitude, and quantal transmitter release were examined at the rat neuromuscular junction in an attempt to identify the functional role of nicotinic receptors on the nerve terminal. TC (50 and 75 nM) significantly depressed the MEPP amplitude but not the amplitude of the initial EPPs during a train-of-six stimulation at 50 Hz. The lack of depression in EPP amplitude by TC was due to an increase in quantal release. The nearly equipotent response of the pre- and post-synaptic effects of TC suggests that the autoreceptors on the nerve terminal are very similar to the nicotinic receptors on the end-plate. These results suggest that nicotinic autoreceptors are functional even with a single action potential. The results support the hypothesis that ACh released from the nerve terminal normally has a negative feedback effect by depressing transmitter release.
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PMID:Nicotinic receptors on the rat phrenic nerve: evidence for negative feedback. 168 73

1. An isolated, buffer-perfused rabbit ear preparation was used to investigate the influence of NG-nitro-L-arginine methyl ester (L-NAME) on endothelium-dependent vasodiltation and modulation of vasoconstrictor responses and vascular conductance. 2. Acetylcholine (0.55 pmol-1.6 nmol) caused dose-related vasodilatation of preparations constricted by the combination of 5-hydroxytryptamine and histamine (both 1 microM), with an ED50 = 31.1 +/- 7.8 pmol and a maximum dilatation of 69.9 +/- 4.3%. In the presence of 10 microM L-NAME the dose-response for vasodilator effects was shifted significantly (P less than 0.001) to the right (ED50 = 3.07 +/- 1.18 nmol) and there was a significant (P less than 0.01) depression of the maximum response (Rmax = 44.3 +/- 4.0%). The higher concentration of 100 microM L-NAME completely abolished vasodilatation to acetylcholine. L-Arginine (10 mM) did not reverse the inhibitory actions of L-NAME at either concentration. 3. L-NAME 100 microM, augmented vascular tone induced by 1 microM 5-hydroxytryptamine and 1 microM histamine, thus altering the characteristics of both pressure/flow and conductance/flow relationships such that conductance was reduced at all flow rates. The augmentation of constrictor tone was reversed in a concentration-dependent manner by L-arginine (10 microM-10 mM) and the effect of L-NAME on the conductance/flow relationships was similarly reversed by 10 mM L-arginine. The augmentation of tone was endothelium-dependent as it did not occur following functional destruction of the endothelium by perfusion of the vascular bed with the detergent CHAPS (0.3%) for 150s. 4. In conclusion, L-NAME is a potent inhibitor of agonist-induced endothelium-dependent vasodilatation. L-NAME reduces vascular conductance in pharmacologically constricted preparations and this emphasizes the important role of EDRF in vascular regulation. The ability of L-arginine to reverse L-NAME-induced inhibition of basal EDRF activity but not L-NAME-induced inhibition of agonistinduced endothelium-dependent relaxations suggests that there is pharmacological heterogeneity in the mechanisms responsible for the conversion of L-arginine to EDRF.
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PMID:Differential effects of L-arginine on the inhibition by NG-nitro-L-arginine methyl ester of basal and agonist-stimulated EDRF activity. 179 35

Brief (5 min) bilateral carotid occlusion in the gerbil produces forebrain ischemia resulting, as previously reported, in almost complete neuronal loss in the CA1 region of the hippocampus; this neuronal destruction occurs between the 4th and 7th day post-ischemia. Various hippocampal biochemical indices were measured from just after such ischemia to 21 days of recirculation, and the temporal pattern of changes compared with that of cell loss. The level of thiobarbiturate reacting substances (TBARS), a measure of lipid peroxidation, was greatly elevated at 30 min after ischemia, rapidly returned to normal levels (by 60 min), but was again elevated on days 4-14. The beginning of this second period of elevation correlated closely with the onset of neuronal loss and the very abrupt and large (to about 32%) decrease in specific N-methyl-D-aspartate (NMDA) binding sites, measured with radioactive CPP. The number of muscarinic binding sites, measured with radioactive quinuclidinyl benzilate, showed an even greater decrease (to 13%) at 21 days post-ischemia, but the decrease was delayed (starting at day 7) and much more gradual than the loss in NMDA binding. In neither case was there any change in binding affinity at any time studied. Acetylcholine (ACh) concentrations were initially greatly decreased (to about 15% at 5 min), transiently increased (to about 130% at 30 min), and then decreased again (to about 15% at 60 min), after which gradual recovery occurred and was completed by day 14. Since no inhibition of choline acetyltransferase activity was observed at any time, the reversible depression in ACh must depend upon some factor other than loss of this key synthetic enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Time course of changes in lipid peroxidation, pre- and postsynaptic cholinergic indices, NMDA receptor binding and neuronal death in the gerbil hippocampus following transient ischemia. 182 14

Experiments were done in isolated, perfused mesenteric vascular beds from Sprague-Dawley rats. Bolus injections of norepinephrine (3-100 nmol) induced dose-dependent increases in perfusion pressure with a maximum increase greater than 100 mm Hg. In the same dose range, clonidine had no effect on perfusion pressure. In the presence of an elevated pressure caused by constant infusions of norepinephrine (6-20 microM), bolus injections of clonidine (0.1-10 nmol) or acetylcholine (0.007-7 nmol) caused dose-related decreases in perfusion pressure. Procedures which damage endothelium (brief exposure to methylene blue or reactive oxygen radicals) abolished the depressor action of acetylcholine but only moderately reduced the depressor action of clonidine. The depressor action of clonidine was not antagonized by the alpha-2 adrenoceptor antagonist, idazoxan. Acetylcholine produced depressor responses in the presence of 5-hydroxy-tryptamine or vasopressin, but clonidine did not. Dose-response curves to bolus doses of norepinephrine were shifted markedly to the right by an alpha-1 selective concentration of prazosin (1 nM) and were shifted to the right with depression of maximum by infusions of clonidine (0.3 and 1.0 microM). It is concluded that, in the mesenteric vasculature of the rat: 1) the role of alpha-2 adrenoceptors, in responses to clonidine, is minimal; 2) endothelial factors play little role, if any, in the depressor effects of clonidine and 3) clonidine has a potent ability to interfere with the alpha-1 adrenoceptor-mediated vasoconstriction induced by norepinephrine. This antagonistic action may be at the level of the receptor but could involve postreceptor steps.
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PMID:Antagonism of norepinephrine by clonidine in the isolated rat mesenteric vascular bed. 194 13

We have examined the effect of perivascular denervation on the ability of acetylcholine to produce endothelium-dependent relaxation in the isolated perfused mesenteric arterial bed. Treatment with capsaicin prevented the development of substance P and calcitonin gene-related peptide containing perivascular nerve fibres. Treatment with 6-hydroxydopamine prevented the development of catecholaminergic perivascular nerve fibres. In the arterial beds from capsaicin treated rats there was a depression of the ability of Acetylcholine to produce endothelium dependent relaxation. No change in endothelium-dependent relaxation to ACh was found in 6-hydroxydopamine treated rats.
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PMID:The effect of perivascular denervation on endothelium-dependent relaxation to acetylcholine. 211 55

The effects of methionine enkephalin (ME) and substance P (SP) were tested on the chemosensory discharge of the cat carotid body-nerve preparation in vitro. ME superfused in concentrations of 10(-8) to 10(-5) M depressed the sensory discharge, an effect followed by receptor excitation (rebound). Bolus applications of ME (30 ng to 3.0 microgram) induced variable effects (excitation or depression) on the discharge, excitation being more pronounced with the smaller doses. Superfusions with SP (10(-8) to 10(-5) M) either excited or depressed the discharge, excitation being more pronounced with higher SP concentrations (i.e. 10(-6) M). Bolus applications of SP (43 ng to 0.5 micrograms) also excited or depressed the sensory discharge. These variations may be dose-dependent. Superfused ME (10(-6) M) significantly depressed the chemoreceptor response to hypoxia (100% N2) and hypercapnia (6% CO2, pH 7.43). The responses to NaCN and acidity (pH 6.0) were marginally depressed. Superfused SP (10(-6) M) clearly depressed the responses to hypoxia, those to hypercapnia and NaCN were marginally affected but the effects of acidity were not altered. When the peptides were tested against the receptor responses to exogenously applied putative neurotransmitters (ACh, dopamine--DA), it was found that ME tended to depress both the ACh and DA actions whereas SP (10(-6) M) tended to increase their effects. Superfusions with naloxone (10(-6) M) increased the basal chemosensory discharge and this enkephalin blocker partially relieved the depressant effect of ME on the ACh-induced response. It is concluded that carotid body chemoreceptors have excitatory and inhibitory reactive sites to both ME and SP although their precise location is still unknown.
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PMID:Effects of methionine-enkephalin and substance P on the chemosensory discharge of the cat carotid body. 241 43


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