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

1. Local conductance changes produced by various bath-applied agonists at frog end-plate membrane were measured using focal recording of extracellular potential in voltage-clamped muscle fibres. The potential difference between a focal micropipette placed on the nerve terminal and another micro-pipette placed on or near inactive membrane was taken as proportional to the agonist-induced current through a small patch of an end-plate membrane. 2. The current-voltage (I--V) relation of active membrane was obtained directly by increasing the membrane potential in a ramp fashion. The change in membrane potential was slow enough for post-synaptic gating processes to reach equilibrium during the ramp. 3. During application of sufficiently low concentrations of full agonists (carbachol, (ACh) and partial agonists (choline and decamethonium) the I--V relation of end-plate membrane showed strong curvature in the range of -60 to -130 mV. The slope of I--V relations increased exponentially with membrane hyperpolarization, an e-fold change in conductance occurring for about 50 mV potential shift. 4. The curvature of the I--V relation of end-plate-membrane activated by the partial agonists choline and decamethonium became less as the agonist concentration was increased, and with high concentrations (choline 15 mM; decamethonium 250 micrometer) the I--V relation became almost straight. 5. When end-plate currents produced by high concentrations of partial agonists were matched by application of equi-active concentrations of carbachol, the carbachol-activated membrane still showed as much curvature in its I--V relation as when low concentrations of carbachol were used. 6. Choline and decamethonium concentrations for which the I--V relation was straight produced much greater depression of miniature end-plate currents than did carbachol concentrations which produced the same membrane current at the holding potential. 7. I--V relations for full agonists at high concentrations were obtained after alpha-bungarotoxin pre-treatment. During application of carbachol (400--500 micrometer) and ACh (30--40 micrometer; after complete inhibition of acetylcholinesterase activity) the I--V relation of end-plate membrane is much less curved than during application of low concentrations. 8. It is concluded that either the voltage sensitivity of agonist-induced end-plate conductance reflects voltage sensitivity of agonist binding, or the partial agonists used can exert a voltage-dependent 'local anaesthetic' action in addition to their agonist activity.
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PMID:A comparison of current-voltage relations for full and partial agonists. 30 43

The action of 21 purine compounds on the twitch response of the electrically stimulated guinea pig isolated ileum has been investigated. Adenosine and related compounds produced a dose-dependent depression of the response. Adenosine was the most potent and 2'-deoxyadenosine had one hundredth the potency of adenosine. Adenine, hypoxanthine, inosine, IMP, ITP, xanthine, xanthosine, XMP, XTP, guanine, GMP and GTP were ineffective at concentrations less than 1 mM. Adenosine (30 microgram) reduced the electrically induced ACh output from the ileal strips. The dose--depression curve for adenosine (0.1--30 microgram) was shifted to the right in the presence of xanthine derivatives and of these, theophylline was the most potent inhibitor of adenosine. On the other hand, dipyridamole (0.1--1 microgram) and hexobendine (0.1--1 microgram) shifted the curve to the left. They markedly inhibited 3H-adenosine uptake into the ileum. Theophylline (0.1 mM), dipyridamole (0.3 microgram) and hexobendine (0.3 microgram) did not affect tetrodotoxin-, adrenaline-, strychnine- and morphine-induced inhibition of the twitch response. The present investigations have revealed that adenosine and related compounds reduce ACh release from the intramural cholinergic nerves in the guinea pig ileum possibly in a specific manner (or through a specific receptor site) different from that of other inhibitors such as morphine.
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PMID:Effects of purine compounds on cholinergic nerves. Specificity of adenosine and related compounds on acetylcholine release in electircally stimulated guinea pig ileum. 63 57

Slices from rat hippocampus, striatum or cortex were incubated with l mum [3H] choline and following 75 min superfusion with Krebs solution the efflux of radioactivity was measured. The slices were stimulated either electrically (1 Hz) or with 25 mM potassium and the rate constant of the evoked release and the size of the releasable pool were estimated. The spontaneous efflux of radioactivity and the releasable pool but not the rate of evoked release correlated with the reported endogenous ACh content of the 3 areas. Raised potassium released radioactivity at a lower rate but from a larger pool than electrical stimulation from all 3 areas. In all 3 areas atropine alone potentiated while physostigmine, oxotremorine and carbamylcholine decreased the rate of evoked release. This depression was fully antagonized by atropine. The drugs had no effect on the size of the releasable pool. Findings suggest that muscarinic receptors located on cholinergic axons or terminals have a physiological role in the autoregulation of ACh release from these 3 areas.
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PMID:The effect of cholinergic drugs on [3H]acetylcholine release from slices of rat hippocampus, striatum and cortex. 84 27

1. The responses of identified cells in the cat Clarke's column and dorsal horn to micro-electrophoretically applied cholinomimetics and anti-cholinergic substances have been investigated. 2. Both antidromically identified (DSCT neurones) and synaptically activated neurones from the region of the Clarke's column of the spinal cord were excited by ACh. However, the proportion of ACh excited cells was greater in units synaptically activated by ipsilateral dorsolateral funiculus stimulation (78%) than in DSCT neurones (50%). In addition, about 55% of neurones activated either antidromically or synaptically by ipsilateral dorsal column stimulation were excited by ACh. 3. In contrast to a relatively weak excitatory potency on the DSCT neurones (maximum firing frequency did not exceed 130% of the control activated by ipsilateral dorsolateral funiculus stimulation (maximum firing frequency reached 430% of the control level). 4. ACh has a relatively quick and rapidly reversible excitatory effect on Clarke's column neurones and some types of dorsal horn interneurones, which can be obtained also with nicotine. However, the action of nicotine is frequently delayed in onset and recovery. This excitatory action of ACh can be blocked or markedly depressed by dihydro-beta-erythroidine. These results and those obtained with acetyl-beta-methylcholine and atropine seem to suggest that the receptors mediating excitation of the cholinoceptive spinal cells activated either antidromically or synaptically by ipsilateral dorsolateral funiculus stimulation besides predominantly nicotinic have also weak muscarinic properties. 5. Desensitization with repeated applications of ACh and nicotine has been observed in both DSCT neurones and units antidromically activated by ipsilateral dorsal column stimulation. 6. About 11% of units antidromically activated by ipsilateral dorsolateral funiculus stimulation were depressed by ACh. In addition, the depressant effect of ACh was more frequently encountered in the cells unresponsive either to the dorsolateral funiculus or dorsal column stimulation. ACh depression was also seen in units activated either antidromically or synaptically by ipsilateral dorsal column stimulation. In contrast, none of the units synaptically activated by the ipsilateral dorsolateral funiculus stimulation were depressed by ACh. The same was true for spinal neurones receiving convergent peripheral inputs activated either antidromically or synaptically by ipsilateral dorsolateral or dorsal column stimulation. 7. The findings that ACh depression of all tested DSCT neurones is blocked by atropine and readily evoked by acetyl-beta-methylcholine indicates that receptors mediating the effect are of muscarinic type.
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PMID:Responses of identified spinal neurones to acetylcholine applied by micro-electrophoresis. 89 42

The carotid body and its own nerve were removed from cats anesthetized with sodium pentobarbital and placed in an air gap system; the carotid body was bathed in modified Locke's solution equilibrated with 50% O2 in N2, pH 7.43 at 35 degrees C. The sensory discharges, changes in "resting" receptor polarization and the mass receptor potential evoked by ACh or NaCN were recorded with nonpolarizable electrodes placed across the gap. Receptor potentials and sensory discharges evoked by ACh showed an appreciable increase in amplitude and frequency when the preparation was bathed in eserinized Locke. Eserine did not change appreciably the responses evoked by NaCN. Excessive depolarization elicited by either ACh or NaCN was accompanied by sensory discharge block. Removal of K+ ions from the bathing solution induced receptor hyperpolarization and an increase in the amplitude of the evoked receptor potentials. An increase of K+ concentration had the opposite effect. Reduction of Na+ or NaCl to one half, or total removal of this salt, induced an initial reduction and later disappearance of the sensory discharges, some receptor hyperpolarization and a reduction in the amplitude of the evoked receptor potential. Reduction or removal of Ca++ produced receptor depolarization, a marked depression of the evoked receptor potentials, an increase in the frequency of the sensory discharges and a reduction in the amplitude of the nerve action potentials. High Ca++ or Mg++ had little or no effect on action potential amplitude or resting polarization, but decreased sensory discharge frequency and the evoked receptor potentials. Total or partial replacement of Ca++ with Mg++ induced complex effects: (1) receptor depolarization which occurred in low Ca++, was prevented by addition of Mg++ ions; (2) the amplitude of the evoked receptor potentials was depressed; (3) the nerve discharge frequency was reduced as it was in high Mg++ solutions; and (4) the amplitude of the nerve action potentials was reduced as it was in low Ca++ solutions. Temperature had a marked effect on the chemoreceptors since at high temperatures the receptors were depolarized and the discharge frequency increased. The baseline discharge and responses evoked by ACh or NaCN were depressed at low temperatures. The results are discussed in terms of possible receptor mechanisms influenced by the different ions.
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PMID:Effects of different ions on resting polarization and on the mass receptor potential of carotid body chemosensors. 97 3

In order to test the hypothesisthat ACh mediates the transmission of pain stimuli from dentin to sensory intradental nerve endings the following experiments were performed. Intradental nerve impulses were recorded by means of low impedance electrodes inserted in dentinal cavities in the tooth of the cat. An air blast proved to be an efficient physical stimulus to excite the intradental nerves. Local application of acetylcholine caused a similar response. This respinse to acetylcholine was followed by a transient blockage to repeated application. The response to acetylcholine could be blocked by d-tubocurarine, atropine, succinylcholine and hexamethonium administered locally. In contrast, the response to physical stimuli (air blasts) could not be blocked by these drugs. Moreover, during the period of depression following acetylcholine the preparation responded to physical stimuli. These findings suggest that acetllcholine is not a mediator in the intradental pain transmission provoked by physical stimuli.
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PMID:The excitatory action of acetylcholine on intradental sensory units. 115 23

(1) The effects of divalent cations (Ca++, Mg++, Sr++ and Co++) were studied on the post-synaptic responses of crustacean neuromuscular junctions and identified molluscan neurons to bath and iontophoretic application of putative transmitters. (2) The glutamate response of the crustacean muscle was parabolically dependent on [Ca++]0, while the ACh response of an identified molluscan neuron was inversely dependent on[Ca++]0. Elevated [Ca++]0 depressed both glutamate and ACh depolarizations in a concentration-dependent, reversible manner. Low concentrations of Co++ also depressed both depolarizations in a concentration-dependent, reversible manner. (3) Double-reciprocal plot analyses of the Ca++ and Co++ depressions indicate that these agents were apparently not acting to reduce the affinity of the receptor for the agonist. Elevated concentrations of both Ca++ and Co++ shifted the inversion potential of the ACh response in a hyperpolarizing direction, suggesting a preferential block of the receptor-coupled Na+ conductance. (4) Neither Ca++ nor Co++ depressed Cl- or K+-dependent responses coupled to the putative transmitters GABA, glutamate, dopamine or ACh. (5) The selective inhibition of the ACh and glutamate responses by the general anesthetic pentobarbital was examined as a function of[Ca++]0. Decreasing [Ca++]0 by 5-fold decreased the pentobarbital inhibition by about 50% while increasing [Ca++]0 by 5-fold produced an insignificant increase in the inhibition. (6) The data indicate that divalent cations, like general anesthetics, selectively depress post-synaptic excitatory responses that are primarily Na+-dependent. This selective depression by Ca++ could contribute to its anesthetic and anticonvulsant properties when present in elevated concentrations in the ventricular fluid. The mechanism by which divalent ions and general anesthetics selectively depress receptor-coupled conductances appear to be different: divalent ions preferentially attack the Na+ component while anesthetics block Na+ and K+ conductance equally (possibly by affecting the kinetics of the mechanism).
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PMID:Divalent cations: effects on post-synaptic pharmacology of invertebrate synapses. 117 55

BW 403C65, an isoquinolinium bisquaternary compound, was investigated for its neuromuscular blocking properties. In vitro in from preparations, low concentrations induced an increase in miniature endplate potentials (m.e.p.p.) frequency without altering their amplitude. With increasing concentrations m.e.p.p. frequency returned to control value and amplitude started to decrease concomitantly with the decreased sensitivity of the endplate to iontophoretically applied acetylcholine and depression of the twitch tension. Acetylcholine released at the neuromuscular junction was also decreased. In vivo in the cat preparation the intra-arterial injection of low doses of the drug produced an increase in the strength of the muscle twitch, and the development of contracture, as well as the appearance of post-drug repetition at the ventral roots. Greater doses produced a progressive decline in post-tetanic potentiation with prolonged return to control.
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PMID:Studies of the neuromuscular blocking effects of BW 403C65 in frog and cat muscle. 119 80

Acetylcholine and nicotine application to the intact pacinian corpuscle failed to stimulate the spike activity, but changed the sensitivity to the mechanical stimulation: low concentration (1.10(-6) g/ml) increased the sensitivity and high concentration (1.10(-4) g/ml) decreased it. This influence can be attributed to the action of these substances on the structures which generate the action potentials. Acetylcholine application to decapsulated pacinian corpuscles stimulated the appearance of the spike activity. This reaction was possibly connected with the acetylcholine influence on the mechanoreceptive zones proper. Tubocurarine or hexonium application of decapsulated pacinian corpuscles led to depression of the sensitivity of the receptor to the mechanical stimulation that can also be explained by the participation of acetylcholine in the process of adequate receptor stimulation.
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PMID:[The effect of cholinergic substances on individual mechanoreceptors--Pacinian corpuscles]. 122 84

We electromagnetically measured blood flow to one cerebral hemisphere and determined cerebrovascular reactivity to vasoconstrictor and vasodilator stimuli during normoglycemia and insulin-induced hypoglycemia in unanesthetized goats. Control blood glucose concentration was 84 +/- 4 mg, and insulin, injected intravenously, decreased glycemia with a concomitant increment in cerebral blood flow and reduction in cerebrovascular resistance in all the animals. When glycemia decreased to 60 to 65 mg/dl, the animals began to show signs of increased adrenergic activity, and when it decreased to less than 30 mg/dl, they showed signs of CNS depression. Cerebral blood flow began to rise significantly at a glycemia of 50 to 55 mg/dl, and progressively increased to reach an increment of 36% +/- 4% when glycemia was less than 30 mg/dl. Norepinephrine (0.3 to 9 micrograms), tyramine (50 to 500 micrograms), and 5-hydroxytryptamine (0.1 to 9 micrograms) reduced cerebral blood flow, and this effect was lower during severe hypoglycemia. Acetylcholine (0.01 to 1 microgram), isoproterenol (0.03 to 3 micrograms), diazoxide (0.3 to 9 mg), and inhalation of 10% CO2 in air increased cerebral blood flow, and this effect was also lower during severe hypoglycemia. The results show that insulin-induced hypoglycemia causes cerebral vasodilation and reduction of the capacity of cerebral blood vessels to constrict and dilate. They also show that the glycemic thresholds for increasing cerebral blood flow are near to, or slightly lower than, the thresholds for hypoglycemic symptoms. This experimental model of hypoglycemia closely resembles the conditions in hypoglycemic patients and permits serial evaluation of the cerebrovascular effects of hypoglycemia without using anesthesia.
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PMID:Effects of hypoglycemia on the cerebral circulation in awake goats. 131 45


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