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

The technique of microelectrophoresis was used to investigate the cholinoceptor pharmacology of spontaneously active single neurones in the parietal cortex of the rat. Acetylcholine, carbachol and the selective M1-muscarinic receptor agonist, McN-A-343, were each potent excitants (rank order of apparent potency: carbachol greater than acetylcholine greater than McN-A-343). When measured in vitro, the apparent mobilities of carbachol and acetylcholine were similar although significantly less than that of McN-A-343, suggesting that the lower potencies of acetylcholine and McN-A-343 probably reflect a genuine biological phenomenon. In addition to excitation, carbachol also evoked biphasic (excitation/depression) and depressant responses. In contrast to the other cholinoceptor agonists, nicotine produced weak and inconsistent excitations. Excitatory responses to acetylcholine and carbachol were significantly attenuated by the selective M1-muscarinic receptor antagonist, pirenzepine, at a time when the excitatory response to McN-A-343 was also significantly reduced. Responses to phenylephrine were not diminished. On several cells an excitatory response to carbachol was converted to a depression by pirenzepine. These results suggest that the excitatory responses of cortical neurones to cholinoceptor agonists are mediated predominantly by M1-muscarinic receptors. The identity of the receptor mediating the depressant response to carbachol remains uncertain, although nicotinic cholinoceptors do not appear to be involved.
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PMID:Involvement of M1-muscarinic receptors in the excitation of neocortical neurones by acetylcholine. 244 71

1. A series of related methylxanthines were studied for their effects on the kinetics of decay of end-plate currents (e.p.c.s) and miniature end-plate currents (m.e.p.c.s) at motor end-plates of the frog. 2. Isobutyl methylxanthine (IBMX, 50 microM-3 mM) produced a concentration-dependent depression of the peak e.p.c. and m.e.p.c. amplitude and a change in the kinetics of e.p.c. and m.e.p.c. decay from the normal single-exponential to a double-exponential function. Drug effects of this nature are generally attributed to open-channel blockade. 3. After wash-out of IBMX, the decay of the e.p.c. or m.e.p.c. was restored to a single-exponential function but with a significantly prolonged time constant. 4. Caffeine or theophylline derivatives (0.1-4 mM), during exposure to drug, produced effects similar to those observed after the application of IBMX; namely a prolongation of the time course of e.p.c.s and m.e.p.c.s without changing the single-exponential nature of the function. 5. Computer simulations were made of the m.e.p.c.s in IBMX. The effects of IBMX could be fitted to the sequential model of channel block only if the prolonged time constant observed upon wash-out was used for the rate constant of channel closure. Independent calculations of the rate constant of channel closure during IBMX application were in agreement with those measured during wash-out. 6. The theophylline derivative 8-phenyltheophylline, a selective adenosine receptor blocker with minimal effects on phosphodiesterase (PDE), increased the time constant of e.p.c. decay in a manner similar to theophylline and caffeine. Non-xanthine PDE inhibitors, either had no effect on m.e.p.c. decay (papaverine) or decreased the time constant of decay (RO 20-1724). It is thus unlikely that PDE inhibition is responsible for the post-junctional effects of IBMX. 7. IBMX (50 microM-2 mM) increased quantal ACh release in the virtual absence of extracellular calcium and also increased the efficacy of adenosine derivatives in inhibiting ACh release. Adenosine (10-100 microM) or 2-chloroadenosine (1-10 microM) had no effect on the time constant of e.p.c. decay nor did these adenosine receptor agonists alter the post-junctional actions of IBMX. The effects of IBMX on end-plate channel kinetics are thus not due to the blockade of adenosine receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Independent control of channel closure and block of open channels by methylxanthines at acetylcholine receptors in frog. 245 Sep 93

1. Acetylcholine (ACh), histamine, prostaglandin E2 and potassium chloride (KCl) each evoked concentration-dependent spasm of guinea-pig isolated trachealis treated with indomethacin (2.8 microM). 2. Neither tetraethylammonium (TEA; 0.1-10 mM) nor procaine (0.1-10 mM) potentiated these spasmogens. Indeed, procaine (10 mM) depressed the log concentration-effect curves of all the spasmogens while TEA (1-10 mM) caused some depression of the log concentration-effect curve of prostaglandin E2. 3. Intracellular electrophysiological recording was performed in trachealis bathed by normal Krebs solution or by Krebs solution containing 2.8 microM indomethacin. In either medium the majority of trachealis cells exhibited spontaneous electrical slow waves while some cells were electrically quiescent. In either medium the spasmogenic effects of ACh (1 mM) and histamine (0.2 mM) were accompanied by depolarization and abolition of slow wave discharge. In many cases the record of membrane potential subsequently exhibited noise which incorporated fast, hyperpolarizing transients. 4. In the absence and presence of indomethacin, TEA (10 mM) and procaine (5 mM) markedly reduced the membrane noise and hyperpolarizing transients evoked by ACh or histamine without augmenting the evoked tension. 5. It is concluded that slow wave discharge does not depend on prostaglandin synthesis. The membrane noise and hyperpolarizing transients evoked by ACh and histamine represent the opening of membrane K+-channels. While such K+-channel opening may offset spasmogen-induced depolarization it does not moderate the evoked tension.
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PMID:Spasmogen action in guinea-pig isolated trachealis: involvement of membrane K+-channels and the consequences of K+-channel blockade. 245 65

Canine and human coronary arteries were studied in organ baths to compare the responses to acetylcholine and serotonin in the two species. The human coronary rings were isolated from seven patients without cardiac disease (mean age 15 years, range 7-20). In one set of experiments canine and human preparations were incubated with phentolamine, propranolol and ketanserin (all at 1 mumol.litre-1 concentration) and precontracted with prostaglandin F2 alpha (PGF2 alpha 1-2 mumol.litre-1). Acetylcholine (0.1-10 mumol.litre-1) and serotonin (0.1-100 mumol.litre-1) relaxed canine preparations dose dependently, the maximum responses (expressed as % of depression of PGF2 alpha response) being 84 (SEM 6)% (n = 9) and 51(5)% (n = 6) respectively. In the same experimental conditions, acetylcholine and serotonin failed to relax the human coronary rings (n = 11) while substance P and bradykinin induced relaxations of 72(4)% (n = 11) and 66(7)% (n = 11) of PGF2 alpha response respectively. In another set of experiments, dose-contraction curves were constructed for acetylcholine or serotonin (in presence of phentolamine and propranolol). On human rings with endothelium, methylene blue (10 mumol.litre-1), a non-specific inhibitor of endothelium derived relaxing factor (EDRF), potentiated these dose-contraction curves: markedly for serotonin, the EC50 decreasing from 1.2(0.2) to 0.22(0.08) mumol.litre-1 (n = 11, p less than 0.01) with a significant increase in the maximal response); and slightly for acetylcholine, EC50 decreasing from 0.84(0.11) to 0.40(0.13) mumol.litre-1 (n = 10, p less than 0.05) without significant change in the maximal response.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of responses to acetylcholine and serotonin on isolated canine and human coronary arteries. 248 33

The effects of phorbol esters on endothelium-dependent relaxations evoked by ACh and the calcium ionophore A23187 were analyzed in isolated canine femoral and coronary arteries mounted in organ chambers or in a bioassay system. In rings of femoral and coronary arteries, phorbol 12,13-dibutyrate (PDBu) (10(-7) M) evoked contraction (ED50 2.9 x 10(-8) M) and depressed endothelium-dependent relaxations to ACh (4-fold increase in ED50 and 72% depression of maximal response). PDBu depressed maximal relaxations to A23187 by 50% but had no effect on ED50. The inactive phorbol ester 4-alpha-phorbol didecanoate (10(-7) M) did not evoke contractions and had no effect on endothelium-dependent relaxations to ACh or A23187. Endothelium-independent relaxations to sodium nitroprusside were not effected by PDBu (10(-7) M) in femoral or coronary arteries. In bioassay experiments, selective treatment of perfused femoral artery segments with PDBu (10(-8)-10(-6) M) caused concentration-dependent inhibition of basal and ACh- (10(-6) M) and A23187-(10(-6) M) induced release of endothelium-derived relaxing factor (EDRF) (as assessed by relaxation of superfused bioassay coronary artery rings without endothelium). PDBu inhibited these responses with different potency: basal (10(-8) M) greater than ACh (10(-7) M) much greater than A23187 (only partial inhibition at 10(-6) M).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phorbol dibutyrate inhibits release and action of endothelium-derived relaxing factor(s) in canine blood vessels. 249 77

The role of G proteins in cholinergic suppression of Ca2+-activated K current was studied in isolated canine colonic myocytes with the whole cell voltage-clamp technique. Acetylcholine (ACh; 10.0 microM) caused a 64 +/- 2.4% depression in the Ca2+-dependent component of the outward current evoked at potentials between -45 and -15 mV when GTP (0.1 microM) was included in the pipette-filling solution. This effect was reversed within 2-4 min on washout of ACh. Without GTP in the filling solution, ACh caused a 15 +/- 2.5% depression in outward current in 60% of the cells tested. When the non-hydrolyzable GTP analogues, GTP gamma S (0.1 mM) or 5'-guanylylimidodiphosphate (GppNHp; 0.1 mM) were used, the decrease in outward current was greater (85 +/- 4.2 and 78 +/- 6.5%, respectively), and it was not reversed on withdrawal of ACh. Dialysis of the cell interior with pipette solution containing pertussis toxin (1 ng/ml) for 30 min had no effect on the whole cell currents evoked on depolarization, but it abolished the effect of ACh on Ca2+-dependent outward current. These data suggest that coupling of muscarinic receptors to the inhibition of Ca2+-activated K channels is mediated by pertussis toxin-sensitive G proteins in colonic smooth muscle cells. G protein-mediated inhibition is distinctly different from the opening of muscarinic-regulated K channels in other cell types.
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PMID:G proteins mediate suppression of Ca2+-activated K current by acetylcholine in smooth muscle cells. 250 60

To obtain information on the sites and mechanisms of the myoneural effect of aminoglycoside and polypeptide type antibiotics, the influence of neomycin, streptomycin, gentamicin and polymyxin B on the depression of the force of contraction (P) of the rat phrenic nerve-hemidiaphragm preparation was investigated at 37 degrees C, 27 degrees C or 17 degrees C and also at 37 degrees C in electrolyte solutions containing 2.5, 1.25 or 0.625 mM CaCl2. Decreasing the temperature or the CaCl2 concentration ((CaCl2)o) of the bath significantly (p less than 0.001) decreased P. The depressant effect of aminoglycosides on P (about 50% of control at 17 degrees C) was increased more with lower temperatures than that of polymyxin B (about 20%). The effect of lowering the (CaCl2)o on the depression of P (about 90% of control at the lowest (CaCl2)o) was about the same with the 4 antibiotics. The development of the maximal effect and the recovery of P after washout was slower with polymyxin B than with the 3 aminoglycosides. 4-Aminopyridine antagonized the depression of P caused by polymyxin B less than that caused by aminoglycosides. The findings suggest that aminoglycosides depress myoneural activity primarily by inhibiting stimulated release of ACh. Polymyxin B also inhibits ACh release, but inhibition of the contraction of myofibrils contributes more significantly to its myoneural effects than with aminoglycosides. It is conceivable that blocking of the ionophores of the postjunctional membrane also contributes to the myoneural effects of polymyxin B.
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PMID:The influence of temperature and calcium concentration on the myoneural effect of antibiotics. 252 Mar 55

The effect of adrenaline (Ad) on muscarinic transmission was examined in B neurones of bullfrog sympathetic ganglia by using intracellular and voltage-clamp recording methods. Bath-application of Ad (5-500 microM) caused a depression of the slow excitatory postsynaptic potential (EPSP) elicited by repetitive stimulations of preganglionic nerve fibres in the presence of curare (30 microM). Ad also depressed the 'muscarinic' ACh potential induced by ionophoretic application of ACh directly to curarized sympathetic neurones in a concentration-dependent manner. Isoprenaline mimicked the effect of Ad in producing the inhibition of the 'muscarinic' ACh potential. Propranolol antagonized the inhibitory action of Ad. Dibutyryl adenosine 3',5'-monophosphate had no significant effect on the 'muscarinic' ACh potential. Under voltage-clamp conditions, Ad caused an inward current associated with inhibition of the M-current (Brown and Adams 1980). Ad depressed the amplitude of slow postsynaptic currents produced by applications of ACh and muscarinic. At a concentration of 100 microM, Ad produced a 68 +/- 8% (n = 12) depression of the amplitude of the muscarinic ACh current. The inhibition of muscarinic transmission induced by Ad is due to a direct suppression of the muscarinic current at the postsynaptic membrane in bullfrog sympathetic ganglia.
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PMID:Adrenaline inhibits muscarinic transmission in bullfrog sympathetic ganglia. 254 82

1. Experiments have been performed with the dual intent of analysing the mechanism by which AH 21-132 relaxes airways smooth muscle and determining whether the effects of this compound can be distinguished from those of theophylline. 2. AH 21-132 (0.25-8 microM) and theophylline (1-1000 microM) each caused concentration-dependent suppression of the spontaneous tone of guinea-pig isolated trachealis. The maximal effect of AH 21-132 was equivalent to that of theophylline. No evidence was obtained that the tissue became sensitized or desensitized to the action of AH 21-132. 3. Propranolol (1 microM) profoundly antagonized the tracheal relaxant action of isoprenaline but not that of AH 21-132. 4. In indomethacin (2.8 microM)-treated tissues, tone was induced by K+-rich (120 mM) Krebs solution, acetylcholine (ACh, 1 mM) or histamine (200 microM). Log concentration-relaxation curves for AH 21-132, isoprenaline and theophylline were all moved to the right in the presence of the spasmogens, the smallest rightward shift being induced by histamine and the greatest by ACh. While maximal effects of AH 21-132 and theophylline were unaffected by the spasmogens, that of isoprenaline was reduced by KCl and ACh. 5. In tissues treated with indomethacin (2.8 microM), AH 21-132 (0.1-100 microM) inhibited the spasmogenic effects of potassium chloride (KCl), ACh and histamine in a concentration-dependent manner. The inhibition was characterized by rightward shifts in the spasmogen concentration-effect curves with depression of their maxima. 6. In tissues treated with both indomethacin (2.8 microM) and ACh (1 mM), the removal of tracheal epithelium caused a small but significant leftward shift in the log concentration-relaxation curve for AH 21-132 but did not alter that for theophylline. 7. In tissues treated with indomethacin (2.8 microM) and maintained at 12 degrees C, theophylline (0.1-3.2 mM) caused concentration-dependent spasm. This effect was not shared by AH 21-132. 8. AH 21-132 (0.1-1000 microM) more potently inhibited the activity of cyclic AMP-dependent than of cyclic GMP-dependent phosphodiesterase derived from homogenates of guinea-pig trachealis. Theophylline, too, inhibited these enzymes but was less potent in each case than AH 21-132 and did not exhibit selectivity for the cyclic AMP-dependent enzyme. 9. It is concluded that AH 21-132 exerts a non-specific (i.e. effective no matter what agent is used to support tone) relaxant effect on the trachealis muscle which does not involve the activation of beta l-adrenoceptors. The profile of the relaxant action of AH 21-132 more closely resembles that of theophylline than that of isoprenaline. However, AH 21-132 can be differentiated from theophylline in that: (a) its relaxant potency is increased by epithelial removal; (b) it does not cause tracheal spasm; (c) it exhibits selectivity as an inhibitor of cyclic AMP-dependent as opposed to cyclic GMP-dependent phosphodiesterase. It is possible that the relaxant effects of AH 21-132 are related to its ability to inhibit cyclic nucleotide phosphodiesterases.
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PMID:Analysis of the relaxant effects of AH 21-132 in guinea-pig isolated trachealis. 255 42

1. Evoked synaptic potentials and currents were recorded in neonatal rat fourth deep lumbrical muscle during the period of polyneuronal innervation. Signs of inhibitory interactions between converging mononeurone terminals were detected. 2. Muscle fibres innervated by axons from the lateral plantar nerve (LPN) and from the sural nerve (SN) were studied. In unblocked preparations the muscle contracted, and electrode tips were mounted on flexible wires to prevent loss of impalements. 3. In voltage recordings from unblocked preparations, paired two-shock stimulation of one nerve revealed synaptic depression: the second response was smaller than the first. When the two stimuli were delivered to different nerves (SN and LPN), the second response was smaller than its own control. 4. In voltage clamped, unblocked preparations, a similar result was obtained. Conditioning stimulation of one nerve (SN, for example) inhibited the response to test stimulation of the other nerve (LPN). The inhibition was greater with larger conditioning responses, was maximal when the conditioning and test stimuli were approximately superimposed, and decayed with a time course of several tens of milliseconds. Several tests showed that the end-plate was well clamped: the observed inhibition could not be explained by voltage escape at the end-plate. 5. The inhibition was not constant during the tail of the test end-plate current (EPC). Instead, it declined during the EPC tail, suggesting that the mechanism of inhibition was active, though diminishing, throughout the time course of the test EPC. 6. The amount of inhibition was not noticeably affected by altering the muscle membrane potential (two cells studied). 7. Treatment with curare or alpha-bungarotoxin to block most ACh receptors reduced the inhibition. In about half of the fibres studied, no inhibition was evident: in the others, up to 50% inhibition was observed. The average inhibition for all receptor-blocked fibres was about 15%. 8. In six alpha-bungarotoxin-treated cells, multiple conditioning stimuli were delivered. In most cases, the amount of inhibition increased with increasing numbers of conditioning stimuli. 9. Several possible mechanisms of inhibition are discussed, including reduction of current through ACh channels during the test response owing to alterations in synaptic cleft ion concentrations produced by the conditioning response, presynaptic inhibition of transmitter release, and postsynaptic receptor saturation.
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PMID:Inhibitory interactions between motoneurone terminals in neonatal rat lumbrical muscle. 257 65


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