ライフサイエンスコーパス: tetracaine

1 ) directly indicate the SR Ca2+ leak (before tetracaine).

2 s were sensitive to block by both Mg(2+) and tetracaine.

3 aradoxically did not modify these actions of tetracaine.

4 an increase of cell Ca2+ during exposure to tetracaine.

5 eviously abolished by the addition of 2.0 mM tetracaine.

6 d relatively high, 1-2 mM, concentrations of tetracaine.

7 a2+ efflux) was increased in the presence of tetracaine.

8 waves that were insensitive to ryanodine or tetracaine.

9 lcium efflux per unit time was unaffected by tetracaine.

10 r the quiescent period following addition of tetracaine.

11 s were dose dependent, from 25 to 200 microM tetracaine.

12 in the presence of various concentrations of tetracaine.

13 odology was developed and demonstrated using tetracaine.

14 versed by traditional RyR inhibitors such as tetracaine.

15 several orders of magnitude more potent than tetracaine.

16 ose observed during perfusion with 50 microM tetracaine.

17 In all cases, tetracaine (0.2 mM) abolished Ca(2+) spark activity, whe

18 Tetracaine (0.75 mM) caused transient complete inhibitio

19 y decreasing ryanodine receptor opening with tetracaine (1 mm).

20 In some experiments, the local anesthetic tetracaine (10 microg) was then microinjected near the A

21 h field-stimulated and voltage-clamped cells tetracaine (100-200 microM) produced an initial decrease

22 iperidine ([(3)H]TCP), [(3)H]ethidium, [(3)H]tetracaine, [(14)C]amobarbital, and 3-(trifluoromethyl)-

23 perchlorate (8.0 mM) or caffeine (0.2 mM) to tetracaine (2.0 mM)-treated fibres, also known to restor

24 Tetracaine (200 microM) reversibly abolished sparks and

25 4-AP and Ba(2+)) but completely inhibited by tetracaine (200 microM), an inhibitor of TREK channels.

26 Here we have synthesized a derivative of tetracaine, 3-[(aminopropyl)amino]-N,N-dimethyl-N-(2-[[4

27 Reduction of RyR2 Ca2+ sensitivity by tetracaine (50 microM) reduced the spontaneous Ca2+ rele

28 ii) blocking Ca(2+) release from the SR with tetracaine, a membrane-permeant, reversible ryanodine-se

29 odulation to detect the interactions between tetracaine, a positively charged small molecule used as

30 At high concentrations (> 1.25 mM), tetracaine abolished all forms of spontaneous release.

31 Resting [Ca2+]i declined 25% after tetracaine addition (126+/-6 versus 94+/-6 nmol/L; P<0.0

32 opical administration of anesthetics such as tetracaine, adrenaline, and cocaine and lidocaine, epine

33 In contrast, inhalation of tetracaine aerosol (mass median aerodynamic diameter of

34 We examined the effect of tetracaine aerosol inhalation, a local anesthetic, on lu

35 Inhalation of tetracaine aerosol resulted in marked reductions in ozon

36 iodophenyl)diazirine ([(125)I]TID) and [(3)H]tetracaine, an aromatic amine, are noncompetitive antago

37 ated channels relative to a multiply charged tetracaine analogue described previously.

38 The tetracaine analogues described here have apparent affini

39 Five new tetracaine analogues were synthesized and evaluated for

40 ding of the noncompetitive antagonists [(3)H]tetracaine and [(3)H]phencyclidine to Torpedo nAChR-rich

41 by acute block of the ryanodine receptor by tetracaine and assessment of the consequent shift of Ca

42 ted, e.g. at a membrane potential of -70 mV) tetracaine and dantrolene each blocked IP3-evoked Ca2+ i

43 the use of blocking drugs such as ryanodine, tetracaine and dantrolene, reportedly specific inhibitor

44 taF/Fo, and FWHM were gradually decreased by tetracaine and increased by caffeine.

45 ermal thresholds to a different extent, with tetracaine and lidocaine being most efficient.

46 , hydrophobic and ionic interactions between tetracaine and lipid molecules predominate.

47 The ryanodine receptor (RyR) blockers tetracaine and Mg(2+) transiently suppressed the frequen

48 perchlorate also reversed the action of 2 mM tetracaine and restored delayed q gamma transients to an

49 Ca(2+) waves and this effect was blocked by tetracaine and ryanodine but not 2-aminoethoxydiphenyl b

50 l to the SLBs decreased the affinity between tetracaine and the bilayers, while this interaction tigh

51 These results indicate that tetracaine and TID bind in a mutually exclusive manner t

52 Although tetracaine and TID bind to the same site, the amine NCAs

53 Only tetracaine and tkP3BzPB, the two agents that had effects

54 s (reducing flux as seen experimentally with tetracaine) and sufficiently rapid intra-SR Ca diffusion

55 receptor (RyR)-specific agents ryanodine and tetracaine, and potentiated by caffeine.

56 from the cell during the burst on removal of tetracaine, and to estimates of the extra calcium gained

57 ]TID analog photoincorporation by NCAs (e.g. tetracaine) as well as identification of the sites of [(

58 (dimethylamino)ethyl 4-(butylamino)benzoate (tetracaine), as well as three large slowly reversible an

59 The SR Ca2+ content was increased by tetracaine, as shown by the integral of the caffeine-evo

60 This may be due to either direct effects of tetracaine at the acetylcholine binding site or preferen

61 This Ca2+ release was initially abolished by tetracaine before returning at a lower frequency, but gr

62 no derivatives inhibiting [(3)H]TCP or [(3)H]tetracaine binding to the resting AChR.

63 ues establishes that the high-affinity [(3)H]tetracaine-binding site is located within the lumen of t

64 photolabeling is at the high-affinity [(3)H]tetracaine-binding site.

65 [(3)H]Tetracaine binds at equilibrium to a single site with a

66 the ion channel, interact competitively with tetracaine but allosterically with TID.

67 phaM2-10 (alphaSer-252) was not inhibited by tetracaine but was enhanced 10-fold by proadifen or phen

68 Before the addition of tetracaine, calculated Ca2+ influx and efflux across the

69 It is concluded that the effects of tetracaine can be accounted for by depression of calcium

70 rmeabilized cat ventricular myocytes, 0.7 mM tetracaine caused almost complete Ca spark inhibition fo

71 At low concentrations (0.25-1.25 mM), tetracaine caused an initial inhibition of spontaneous r

72 olabeling as well as its dependence on [(3)H]tetracaine concentration establish that the observed pho

73 The plots of maximum charge against tetracaine concentration suggested a saturable 1:1 drug

74 kinetics, even the micromolar (0.05-0.2 mM) tetracaine concentrations that failed to markedly alter

75 The micromolar tetracaine concentrations that were hitherto reported to

76 sation of the SR Ca2+ release mechanism with tetracaine decreased the frequency of spontaneous releas

77 Infusions of 2% tetracaine did not impair acquisition of the response or

78 nsiently less than influx and, on removal of tetracaine, efflux was greater than influx.

79 On adding tetracaine, efflux was transiently less than influx and,

80 stingly, the potency of the local anesthetic tetracaine for the inhibition of alpha3beta4 and alpha3b

81 ditioned response was notably reduced in the tetracaine group (M = 0.40, SEM +/- 0.216) relative to t

82 e channels incorporated into lipid bilayers, tetracaine (> 0.25 mM) induced a steady inhibition of ch

83 ion sessions, an artificial tear solution or tetracaine hydrochloride was administered to the cornea

84 red saline nasal spray bilaterally, or (2) a tetracaine hydrochloride-oxymetazoline hydrochloride nas

85 Tetracaine hydrochloride-oxymetazoline nasal spray appea

86 50 = 4 muM) than in the resting state ([(3)H]tetracaine; IC50 = 60 muM), whereas it bound with only v

87 eviously abolished by the addition of 2.0 mM tetracaine in common with previous results of using ryan

88 revented by injection of a local anesthetic (tetracaine) in the cloacal region prior to courtship and

89 As expected, bilateral tetracaine inactivation of the hippocampus disrupted spa

90 times and burst durations, mecamylamine and tetracaine induced unique subconductance states.

91 The tetracaine-induced decline in [Ca2+]i and increase total

92 The low affinity inhibitor tetracaine induces a decrease in the extent of release t

93 bsence of agonist (resting state), there was tetracaine-inhibitable photolabeling of amino acids in t

94 Tetracaine inhibited [(125)I]TID labeling of M2-9 and M2

95 Spermidine or tetracaine inhibited cleavage of bacterial membranes by

96 Spermidine and tetracaine inhibited PLA2 activity and spermidine protec

97 olecule motility assay, the local anesthetic tetracaine inhibited the motility of individual kinesin

98 ne receptor (RyR) antagonists (ryanodine and tetracaine) inhibited both sparks and waves but increase

99 adequate to alter the voltage dependence of tetracaine inhibition, both point mutations are required

100 ChR is mediated by a steric mechanism; (iii) tetracaine inhibits CrV binding to the resting AChR, pro

101 ggest that the highly charged moiety of APPA-tetracaine interacts strongly with the negative charge c

102 ults in specific photoincorporation of [(3)H]tetracaine into each nAChR subunit.

103 We propose that the partitioning of tetracaine into solid-gel membranes is determined primar

104 Microinjection of GABA or tetracaine into the medullary nucleus gigantocellularis

105 Infusions of 2% tetracaine into the prelimbic-infralimbic areas did not

106 Infusions of 2% tetracaine into the prelimbic-infralimbic or dorsal ante

107 Amethocaine, tetracaine, iontophoresis, and the S-caine patch, a prod

108 [(3)H]Tetracaine is a noncompetitive antagonist of the Torpedo

109 n of release by submaximal concentrations of tetracaine is caused by a gradual increase in SR Ca2+ lo

110 gated ion channels, and the local anesthetic tetracaine is known to block CNG channels in a manner th

111 ibition of alpha3beta4(6'F10'T) receptors by tetracaine is unaffected by membrane voltage, and at con

112 h that maximally effective concentrations of tetracaine isolate a single distinct species of conserve

113 c effect was also negated by coinfusion with tetracaine, molecular and pharmacologic inhibition of NR

114 Tetracaine (N,N-dimethylaminoethyl-4-butylaminobenzoate)

115 and cocaine and lidocaine, epinephrine, and tetracaine offers the advantage of replacing lidocaine i

116 separate kinetic and steady-state effects of tetracaine on intramembrane charge movements, at micromo

117 fluorometry was used to study the effects of tetracaine on spontaneous Ca2+ release from the sarcopla

118 icked the transient and sustained effects of tetracaine on spontaneous Ca2+ release.

119 We conclude that the primary effect of tetracaine on SR Ca(2+)-release channels is inhibition o

120 The effects of graded concentrations of tetracaine on the steady-state and kinetic properties of

121 Caffeine also antagonized the actions of tetracaine on the total available qgamma charge, but did

122 We suggest that, in tetracaine or acidosis, the initial phase of the Ca2+ tr

123 were attenuated by microinjection of either tetracaine or cobalt into sites near the A7 cell group n

124 Similar injections of tetracaine or cobalt more than 500 microm from the A7 ne

125 depressing RyR open probability (P(o)) with tetracaine or intracellular acidification.

126 urate analogs inhibited the binding of [(3)H]tetracaine or photoincorporation of 3-trifluoromethyl-3-

127 in a junctional cluster (which is reduced by tetracaine or ruthenium red) and other SR Ca handling pr

128 of ryanodine receptors (RyRs) are blocked by tetracaine or ruthenium red, Ca sparks lasting hundreds

129 ty labeled by [(125)I]TID in the presence of tetracaine, PCP, or HTX.

130 Removal of tetracaine produced a transient overshoot of contraction

131 significant block of Na(+) channels by APPA-tetracaine required concentrations of hundreds of nanomo

132 1 drug binding that spared a fixed amount of tetracaine-resistant (q beta) charge but inhibited a dis

133 ained at the reduced values expected for the tetracaine-resistant qbeta charge.

134 Exposure of the myocytes to tetracaine resulted in a gradual increase in the SR Ca2+

135 nAChR-rich membranes equilibrated with [(3)H]tetracaine resulted in covalent incorporation with simil

136 ut recovery after incubation with 300 microM tetracaine resulted in SR Ca(2+) release with no coheren

137 positive charge at the tertiary amine end of tetracaine results in higher potency and voltage depende

138 nAChR-rich membranes equilibrated with [(3)H]tetracaine results in specific photoincorporation of [(3

139 Tetracaine reversed the effects of caffeine but not of r

140 Tetracaine's effective pK(a) was reduced by 0.3-0.4 pH u

141 Tetracaine's location in the membrane placed the drug's

142 Tetracaine's location within the membrane (as indicated

143 nteractions are the critical determinants of tetracaine's location.

144 arget ryanodine receptors (RyR1: dantrolene, tetracaine, S107) and L-type Ca(2+) channels (LTCCs: nif

145 Nevertheless, a complete inhibition of a tetracaine-sensitive (q gamma) charge movement by 2 mM t

146 nd substantial I(K1), but no temperature- or tetracaine-sensitive K(+) currents.

147 Abrupt block of SR Ca2+ leak by tetracaine shifts Ca2+ from the cytosol to SR.

148 and was the same for neutral and protonated tetracaine, showing that the dipole-dipole and hydrophob

149 With all four subunits contributing to [(3)H]tetracaine site, the site in the closed channel state of

150 he isolated peptides demonstrated that [(3)H]tetracaine specifically labeled two sets of homologous h

151 R subunit specifically photolabeled by [(3)H]tetracaine that contribute to the high-affinity binding

152 These parallel earlier effects of tetracaine that have been reported upon the transient an

153 -sensitive (q gamma) charge movement by 2 mM tetracaine that left only q beta charge, sharply altered

154 yl]oxy]ethyl )propan-1-aminium acetate (APPA-tetracaine), that contains three positively charged amin

155 hifts of fluorescence emission at high lipid:tetracaine, the corresponding increases in fluorescence

156 On removal of tetracaine there was an increase of the Na+-Ca2+ exchang

157 On removal of tetracaine, there was a burst of spontaneous Ca2+ releas

158 cell, allowing for various concentrations of tetracaine to be introduced over the surface in a buffer

159 ) was still observed after pretreatment with tetracaine to block Ca(2+) release from ryanodine recept

160 In the presence of tetracaine to eliminate Ca(2+) release from ryanodine re

161 binding of the noncompetitive antagonist [3H]tetracaine to nAChR-rich membranes (IC50 = 150 microM).

162 The ability of tetracaine to reduce spark magnitude suggests that these

163 xposed to 0 Na+, 0 Ca2+ solution +/-1 mmol/L tetracaine (to block resting leak).

164 Tetracaine-treated females had accumulation patterns sim

165 of fluorescence intensity of membrane-bound tetracaine (TTC) on solution pH.

166 n the similar burst on removal of 100 microM tetracaine v/sigma was higher than control (166 +/- 9 %,

167 ransient decrease of contraction produced by tetracaine was accompanied by a small transient increase

168 The q beta charge thus isolated by 2 mM tetracaine was conserved through a wide range of applied

169 In contrast, the RyR2 blocker tetracaine was equally efficacious in mutant Purkinje ce

170 e sarcoplasmic reticulum (SR) measured using tetracaine was significantly increased in diabetic myocy

171 by blocking ryanodine receptors (RyR2) with tetracaine, was approximately 50% higher in cAF versus c

172 SR Ca(2+) increased as [ATP] was reduced or [tetracaine] was increased.

173 The effects of tetracaine were examined on rat ventricular myocytes.

174 The effects of tetracaine were studied on voltage-clamped rat ventricul

175 nAChR-rich membranes photolabeled with [(3)H]tetracaine were subjected to enzymatic digestion, and pe

176 tifungal (tolnaftate), and local anesthetic (tetracaine), were examined.

177 Co-infusion of the local anesthetic tetracaine with duodenal lipids abolished the lipid-indu

178 Interactions of the local anesthetic tetracaine with unilamellar vesicles made of dimyristoyl