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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the present study, augmentation of contractile responses to acetylcholine, potassium chloride and caffeine by prostaglandin F2 alpha on frog rectus abdominis muscle is documented. The PG-induced responses to ACh was restricted to brief exposure of the tissue to PG. Prolonged exposure resulted in disappearance of the enhancing effect and depression of ACh responses. The augmentation of ACh response was unaltered in presence of physostigmine and the pA2-value of d-tubocurarine was not changed by PGF2 alpha ruling out the involvement of a cholinergic mechanism. In potassium depolarized muscle, PGF2 alpha abolished the contractile response to caffeine, indicating an action at the trigger calcium site. PGF2 alpha also permitted reactivation contracture during repolarization.
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PMID:PGF2 alpha on drug-induced contractile responses of frog rectus abdominis muscle. 696 69

1. The myenteric plexus-longitudinal muscle preparation of the guinea-pig ileum was incubated with [(3)H]choline (1.125-1.5 muM), and then superfused with Tyrode solution containing hemicholinium-3 (10 muM). Secretion of [(3)H]acetylcholine ([(3)H]ACh) was evoked either (a) by electrical field stimulation (0.5-15 Hz, 150 shocks per period, 0.5 msec), used to ;indirectly' depolarize the varicosities of nerve terminals, or (b) by high potassium (40 mM with 1 muM-tetrodotoxin, for 6 min, or 80 mM without tetrodotoxin, for 1 min), to ;directly' depolarize varicosities.2. With these stimulation parameters, which yielded about the same fractional secretion of [(3)H]ACh, and with eserine (10 muM) present in the medium, atropine (1 muM) enhanced the ;indirectly', electrically evoked secretion 3.65+/-0.34 (n = 6) fold, and that caused by 40 mM or 80 mM-potassium 1.82+/-0.06 (n = 6) or 1.55+/-0.09 (n = 10) fold, respectively. Atropine thus enhanced ;indirectly', electrically evoked secretion 4-fold more than that caused by ;direct' depolarization of varicosities with high potassium (P < 0.001).3. This difference is not likely to be caused by depression of the sensitivity of the presynaptic muscarinic receptors to ACh released by nerve stimulation, caused by the hypertonicity of the medium in the potassium stimulation experiments. The medium made hypertonic by addition of Tris-HEPES (80 mM) did lower the binding affinity of membrane preparations of (pre- and post-synaptic) muscarinic receptors, to carbamylcholine, and also the contractile responsiveness of the longitudinal muscle to this agent, in both cases to about one half. But it did not appear to alter the responsiveness of either pre- or post-synaptic muscarinic receptors to endogenous ACh, released by nerve stimulation.4. The results support a dual-mode model for the muscarinic negative feed-back control of ACh secretion from the nerve terminals of this preparation, mainly operating by restriction of the invasion of terminals, and only secondarily by depression of the efficiency of depolarization-secretion coupling in invaded varicosities.5. Since this model has earlier been proposed to apply for the control of secretion of [(3)H]noradrenaline from the micro-anatomically similar nerve terminals of noradrenergic nerves, the present findings suggest that the model may have a wider biological significance, and possibly apply to the control of the secretory activity of boutons-en-passant nerve terminals in general.
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PMID:The effects of atropine on [3H]acetylcholine secretion from guinea-pig myenteric plexus evoked electrically or by high potassium. 714 61

We performed experiments to determine whether or not acetylcholine exerts a prejunctional inhibitory effect on adrenergic neurotransmission in the human blood vessel wall. Rings of human greater saphenous veins were prepared 2 to 15 hours after death and mounted for isometric tension recording in organ chambers filled with Krebs-Ringer solution. Acetylcholine depressed contractile responses to electric activation of the sympathetic nerve endings significantly more than those to exogenous norepinephrine; the relaxations caused by the cholinergic transmitter were antagonized by atropine. Helical strips were incubated with [3H]norepinephrine and mounted for superfusion. Electric stimulation augmented the fractional release of labeled norepinephrine. Acetylcholine caused a depression of the evoked 3H release which was antagonized by atropine but not by hexamethonium. These experiments demonstrate that, as in animal cutaneous veins, there are prejunctional inhibitory muscarinic receptors on the adrenergic nerve endings in the human saphenous vein. By contrast, the human vein also contains postjunctional inhibitory muscarinic receptors.
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PMID:Prejunctional inhibition of norepinephrine release caused by acetylcholine in the human saphenous vein. 724 70

Motoneurons undergo a phase of target-dependent cell death during development. In chick embryos, motoneuronal death is blocked by the application of the nicotinic antagonists d-tubocurare (dTC) or alpha-bungarotoxin (alpha BTX). Paralytic doses of these drugs also increase intramuscular nerve branch formation. To investigate the possibility that a neuronal rather than a muscle-type nicotinic ACh receptor (nAChR) might be responsible for the toxin-induced arrest of naturally occurring motoneuronal death, we compared the doses of dTC and alpha-BTX required for paralysis with those needed to protect motoneurons from cell death. We also measured the effects of dTC on the survival of retrogradely labeled motoneurons in culture, and of various doses of dTC on intramuscular nerve branch formation. Subparalytic doses of dTC caused small but significant increases in nerve branch number, while higher doses produced larger effects. In contrast, motoneuronal survival was already maximal at doses of dTC or alpha-BTX below those needed for a visible effect on limb movement. Moreover, dTC increased motoneuron survival in culture, in the absence of muscle cells and muscle-type nAChRs. Nicotinic blocking agents can therefore rescue motoneurons with minimal depression of neuromuscular transmission, suggesting that this effect may be mediated through neuronal, rather than muscle-type.
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PMID:The nicotinic blocking agents d-tubocurare and alpha-bungarotoxin save motoneurons from naturally occurring death in the absence of neuromuscular blockade. 747 8

The effect of activation of cholinergic receptors on long-term potentiation (LTP) in rat piriform cortex pyramidal cells was studied using extracellular and intracellular recordings in brain slice preparations. The functional role of this modulation was studied in a realistic network biophysical stimulation. Repetitive stimuli were applied in two paradigms: one in which the recorded cell was held at its resting potential and one in which synaptic activity was superimposed on a depolarizing pulse strong enough to evoke four action potentials. In the absence of cholinergic modulation, stimulation at 5 Hz induced LTP primarily in the second condition (13.7%, n = 6 out of 9, measured at 10 min after tetanus). When stimuli were applied in the presence of the muscarinic agonist carbachol (20 microM), LTP of greater amplitude was induced in both paradigms (resting: 41.5%, n = 11 out of 16, depolarized: 36%, n = 5 out of 7, measured at 10 min after tetanus). Increases in excitatory postsynaptic potential (EPSP) amplitudes in the presence of carbachol were gradual, starting at the time 5 Hz stimuli were applied and continuing until an action potential was evoked synaptically. In the presence of the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV), LTP could not be induced. The muscarinic antagonist atropine also prevented LTP induction in the presence of carbachol. Cholinergic modulation of synaptic plasticity was examined in a previously developed realistic biophysical network simulation. In simulations, use of a gradual rate of synaptic modification prevented excessive strengthening of synapses, which could cause interference between stored patterns. The effect of excess synaptic strengthening can be avoided by introducing activity dependent depression of synaptic strength. Coactivation of learning and depression rules results in a stable system where no interference occurs, at any rate of learning. Implementing the depression rule only during recall does not improve the network's performance. This implies that reduction in the strength of synaptic connections should occur in the presence of ACh, more than in normal conditions. We propose that two effects of ACh--enhancement of LTP and enhancement of LTD--should act together to increase the stability of the cortical network in the process of acquiring information.
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PMID:Cholinergic modulation of activity-dependent synaptic plasticity in the piriform cortex and associative memory function in a network biophysical simulation. 747 21

The modulation of acetylcholine-activated current (IACh) by protein kinase C (PKC) was studied in Xenopus laevis oocytes microinjected with either mRNA extracted from C2C12 myotubes (C2C12 mRNA) or RNAs encoding murine alpha beta gamma delta subunits of the nicotinic ACh receptor (nAChR). Voltage-clamped oocytes were treated for 90 sec with 12-O-tetradecanoylphorbol-13-acetate (TPA, 300 nM), a potent PKC activator. Transient increase in the amplitude and acceleration in the decay of IACh were invariably observed within minutes of TPA application, and were independent of extracellular Ca2+ concentration. Both parameters recovered to control within 20-30 min; then a slight depression of IACh developed. By this time, an initial PKC down regulation was observed. At the peak of TPA-induced potentiation, dose-response relations suggested an increased binding affinity of nAChR for the neurotransmitter. 4 alpha-phorbol 12,13-didecanoate (300 nM), a biologically inactive analogue of TPA, did not affect IACh, while staurosporine (5-10 microM), a potent inhibitor of PKC activity, suppressed the action of TPA on IACh. In oocytes co-injected with C2C12 mRNA and with rat brain mRNA, IACh was potentiated by 5-hydroxy-tryptamine (10 microM), whose receptors are coupled to phosphoinositide hydrolysis. The nAChR-channel activity in cell-attached patches increased when TPA was applied to the oocytes. In 50% of the oocytes examined, a sustained depression of the single channel activity followed. We conclude that in Xenopus oocytes an endogenous PKC system regulates the function of embryonic-type muscle nAChRs.
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PMID:Protein kinase C modulates exogenous acetylcholine current in Xenopus oocytes. 747 75

1. The effects of NG-nitro-L-arginine methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA), their D-isomers, and dexamethasone on noradrenaline (NA)-induced contractions and antagonism by alpha-adrenoceptor antagonists, have been investigated in rat isolated thoracic aortic rings with/without endothelium. 2. NA produced concentration-dependent contractions of isolated aortic rings with EC50 values of 2.41 +/- 0.54 (n = 21) and 28.00 +/- 8.50 (n = 25) nM for endothelium-denuded and -intact preparations respectively. Acetylcholine (ACh) relaxed NA-precontracted rings with intact, but not those denuded of endothelium. 3. Treatment with L-NAME (1-30 microM), or L-NMMA (10-500 microM), but not their D-isomers, resulted in an endothelium-dependent enhancement of NA-induced contractions. Pre-treatment, in vitro, with 0.5 microM dexamethasone neither directly potentiated, nor influenced L-NAME-induced potentiation of NA-mediated contractions in endothelium-intact rings; however, dexamethasone pretreatment reduced EC50 values for NA, and also prevented L-NAME-induced potentiation, in denuded rings equilibrated for 5 h under resting tension. 4. In both intact and denuded rings, phentolamine, prazosin and WB 4101 shifted NA concentration-response curves to the right; L-NAME, and also L-NMMA, but not their D-isomers, reversed the blockade as indicated by significant decreases in NA dose-ratios. In denuded rings, reversal by L-NAME or L-NMMA was prevented following pretreatment with dexamethasone. 5. Following treatment with 5 or 50 nM phenoxybenzamine (PBZ), NA concentration-response (C-R)curves were shifted to the right with marked depression of maximal responses; 100 microM L-NAME reversed the antagonism in both endothelium intact and denuded rings. However, 500 nM PBZ treatment resulted in complete abolition of the responses to NA, and contractions were not restored by either L-NAME or L-NMMA.6. 5-Hydroxytryptamine (5-HT)-induced contractions of aortic rings were potentiated by endothelium denudation and also by L-, but not D-, NAME. 5-HT-induced contractions were non-competitively antagonized by 10nM ritanserin, and 100 microM L-NAME partially reversed the antagonism in intact but not denuded rings.7. It is concluded that the inhibition of constitutive endothelial NO synthase and inducible smooth muscle NO synthase accounts for the ability of L-NAME, and L-NMMA, to potentiate the effects of agonists and reduce alpha-adrenoceptor antagonism in endothelium-intact and denuded rings. Furthermore,endothelial cell removal/damage triggers the induction of a smooth muscle NO synthase.
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PMID:Interactions of nitric oxide synthase inhibitors and dexamethasone with alpha-adrenoceptor-mediated responses in rat aorta. 768 95

Rabbit atria were isolated with the extrinsic right sympathetic and vagus nerves attached and perfused with Tyrode solution. Acetylcholine overflow was determined after labelling of the transmitter stores with [14C]choline and fractionation of the radioactivity on cation exchange columns. Sympathetic nerve stimulation (SNS, 2 Hz, 3 min) carried out together with vagus nerve stimulation (VNS, 2 Hz, 3 min), but each SNS pulse preceding a vagal one by 19 ms, caused a facilitation of acetylcholine overflow of about 60% versus independent controls in the absence of SNS. Antagonists of putative neurotransmitters were tested to find out the prejunctional mediator involved in the facilitation. The facilitation was not significantly reduced by prazosin, rauwolscine, idazoxan, or propranolol, excluding mediation by alpha- or beta-adrenoceptors. However, guanethidine abolished evoked noradrenaline release and facilitation, suggesting that it is due to a compound co-released with noradrenaline from postganglionic noradrenergic nerves. Pretreatment of rabbits with reserpine which reduced noradrenaline content of atria and SNS evoked overflow by 94% did not affect the facilitation of acetylcholine release which, due to the cardiostimulatory action of SNS being absent, resulted in enhanced depression of atrial force. We conclude that the facilitation is due to release of a reserpine-resistant co-transmitter from sympathetic nerves. Possible mediation of the facilitation by ATP through P2X- or P2Y-purinoceptors was excluded by ineffectiveness of alpha, beta-methylene ATP-preperfusion, of suramin and cibacron blue, respectively. However, the selective A2 adenosine receptor antagonist CP 66,713 reduced the facilitation by 25% whereas DPCPX (A1-selective) had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Co-transmitter mediated facilitation by sympathetic nerve stimulation of evoked acetylcholine release from the rabbit perfused atria preparation. 777 98

1. Comparison between the chronotropic and inotropic effects induced by nicotine in the right and left atrial muscles of rat was investigated. 2. Nicotine (300 microM and 1 mM) significantly produced negative chronotropic and inotropic effects in the right atrium. The effects were concentration-dependent, and reached a maximum about 30 sec after nicotine administration (1 mM). The responses were attenuated with time even during exposure to nicotine (desensitization). 3. In the left atrium, nicotine (300 microM and 1 mM) caused a negative inotropic effect. The depression was decreased with an increase in the frequencies of stimulation (1-3 Hz). The negative inotropic effect reached a maximum at approx. 60 sec later. 4. Nicotine (1 mM) caused a greater negative inotropic response in the right atrium than in the left atrium by 23% (stimulated at 3 Hz). The effects were not modified by atropine (1 microM) and hexamethonium (1 mM). 5. There was no difference between single and cumulative administrations of nicotine in both right and left atrial muscles. 6. These results suggest that the negative chronotropic and inotropic effects of nicotine may be due mainly to a direct action on the cell membrane of rat atria, accompanied with down regulation of nicotinic ACh receptors. The difference between the right and left atria could result from a different innervation of the autonomic nervous system.
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PMID:Negative chronotropic and inotropic responses to nicotine in rat right and left atria. 783 29

Effects of several acyclic eicosanoids (which are formed from arachidonic acid under the action of 5- and 12-lipoxygenases) on desensitization of somatic cholinoreceptors of Helix lucorum RPa3 and LPa3 neurons were studied by means of two-electrode voltage clamp technique. The substances under study were: leukotrienes B4, C4, 12(S)-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoic acid (12-HETE), threo- and erythro-epimers of hepoxilin B3. Cholinoreceptor plasticity was evaluated by a degree of depression of inward current, induced by rhythmical local ACh applications on the soma with intervals 55-180 sec. Leukotrienes B4 and C4 intensified cholinoreceptor plasticity. Inhibitor of inositol-1,4,5-trisphosphate-dependent (IP3-d) mobilization of deposited Ca2+, TMB-8, prevented the effect of leukotriene C4. 12-HETE, threo- and erythro-epimers of hepoxilin B3 did not change plasticity. A conclusion is made that cholinoreceptor plasticity is controlled by leukotrienes B4 and C4. One of the regulatory pathways includes IP3-d Ca-mobilization. Eicosanoids from 12-lipoxygenase pathway (12-HETE, threo- and erythro-epimers of hepoxilin B3) do not participate in this intracellular regulatory mechanism.
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PMID:[The effect of leukotrienes B4, C4, 12-hydroxyeicosatetraenoic acid and of the threo- and erythro-epimers of hepoxilin B3 on the plasticity of the neuronal cholinoreceptors in the snail]. 794 21


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