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Article: Treatment of hypertension with oral taurine: experimental and clinical studies.

Militante, J D / Lombardini, J B

2002 Volume 23, Issue 4, Page(s) 381–393

Abstract: Oral taurine treatment has been studied extensively as a hypotensive agent. Several rat models of hypertension have been used to prove that dietary taurine supplementation can alleviate high blood pressure, among other cardiovascular problems. ... ...

Abstract	Oral taurine treatment has been studied extensively as a hypotensive agent. Several rat models of hypertension have been used to prove that dietary taurine supplementation can alleviate high blood pressure, among other cardiovascular problems. Experimental models mentioned in this review are the spontaneously hypertensive rat, the DOCA-salt rat, the Dahl-S rat, the renovascular hypertensive rat, the hyperinsulinemic rat and the ethanol-treated rat. The beneficial effects of taurine were also demonstrated in studies involving human subjects suffering essential hypertension. Taurine supplementation of 6 g/day for as little as 7 days resulted in measurable decreases in blood pressure in these patients. In both rat and human studies, the effects of taurine appeared to be dependent on the modulation of an overactive sympathetic system. However, taurine has positive effects on other types of cardiovascular problems and thus may act through more than one mechanism.
MeSH term(s)	Administration, Oral ; Animals ; Blood Pressure/physiology ; Central Nervous System/metabolism ; Disease Models, Animal ; Humans ; Hypertension/drug therapy ; Hypertension/etiology ; Hypertension/metabolism ; Rats ; Rats, Inbred Strains ; Taurine/administration & dosage ; Taurine/metabolism ; Taurine/therapeutic use
Chemical Substances	Taurine (1EQV5MLY3D)
Language	English
Publishing date	2002
Publishing country	Austria
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1121341-3
ISSN	1438-2199 ; 0939-4451
ISSN (online)	1438-2199
ISSN	0939-4451
DOI	10.1007/s00726-002-0212-0
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Article: Characterization of taurine uptake in the rat retina.

Militante, J D / Lombardini, J B

Advances in experimental medicine and biology

2000 Volume 483, Page(s) 461–467

MeSH term(s)	Alkaloids ; Animals ; Benzophenanthridines ; Dose-Response Relationship, Drug ; Enzyme Inhibitors/pharmacology ; Phenanthridines/pharmacology ; Protein Kinase C/antagonists & inhibitors ; Rats ; Retina/drug effects ; Retina/metabolism ; Rod Cell Outer Segment/drug effects ; Rod Cell Outer Segment/metabolism ; Taurine/analogs & derivatives ; Taurine/pharmacokinetics ; Taurine/pharmacology
Chemical Substances	Alkaloids ; Benzophenanthridines ; Enzyme Inhibitors ; Phenanthridines ; Taurine (1EQV5MLY3D) ; taurocyamine (543-18-0) ; chelerythrine (E3B045W6X0) ; Protein Kinase C (EC 2.7.11.13)
Language	English
Publishing date	2000
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/0-306-46838-7_51
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Article: Effects of calmodulin antagonists on taurine-stimulated calcium ion uptake in the rat retina are partly independent of calmodulin activity.

Militante, J D / Lombardini, J B

Advances in experimental medicine and biology

2000 Volume 483, Page(s) 477–485

MeSH term(s)	Adenosine Triphosphate/metabolism ; Animals ; Calcium/pharmacokinetics ; Calcium Chloride/pharmacokinetics ; Calmodulin/antagonists & inhibitors ; Cations, Divalent ; Naphthalenes/pharmacology ; Rats ; Rats, Sprague-Dawley ; Rod Cell Outer Segment/drug effects ; Rod Cell Outer Segment/metabolism ; Sulfonamides/pharmacology ; Taurine/pharmacokinetics ; Taurine/pharmacology ; Trifluoperazine/pharmacology
Chemical Substances	Calmodulin ; Cations, Divalent ; Naphthalenes ; Sulfonamides ; N-(8-aminooctyl)-5-iodonaphthalene-1-sulfonamide (103771-14-8) ; Taurine (1EQV5MLY3D) ; Trifluoperazine (214IZI85K3) ; Adenosine Triphosphate (8L70Q75FXE) ; Calcium Chloride (M4I0D6VV5M) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2000
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/0-306-46838-7_53
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Article: Calcium uptake in the rat retina is dependent on the function of the cyclic nucleotide-gated channel: pharmacologic evidence.

Militante, J D / Lombardini, J B

Advances in experimental medicine and biology

2000 Volume 483, Page(s) 469–476

MeSH term(s)	Adenosine Triphosphate/metabolism ; Adenosine Triphosphate/pharmacology ; Aminoquinolines/pharmacology ; Animals ; Cadmium/pharmacology ; Calcium/pharmacokinetics ; Calcium Channel Blockers/pharmacology ; Calcium Channels/physiology ; Calcium Chloride/pharmacokinetics ; Cyclic GMP/analogs & derivatives ; Cyclic GMP/pharmacology ; Cyclic GMP-Dependent Protein Kinases/antagonists & inhibitors ; Cyclic Nucleotide-Gated Cation Channels ; Guanylate Cyclase/antagonists & inhibitors ; Ion Channels/antagonists & inhibitors ; Ion Channels/physiology ; Rats ; Retina/drug effects ; Retina/metabolism ; Rod Cell Outer Segment/drug effects ; Rod Cell Outer Segment/metabolism ; Taurine/metabolism ; Taurine/pharmacology ; Thionucleotides/pharmacology
Chemical Substances	Aminoquinolines ; Calcium Channel Blockers ; Calcium Channels ; Cyclic Nucleotide-Gated Cation Channels ; Ion Channels ; Thionucleotides ; Cadmium (00BH33GNGH) ; 8-bromo-beta-phenyl-1,N(2)-ethenoguanosine 3',5'-cyclic monophosphorothioate (172806-21-2) ; Taurine (1EQV5MLY3D) ; Adenosine Triphosphate (8L70Q75FXE) ; 6-anilino-5,8-quinolinedione (91300-60-6) ; Cyclic GMP-Dependent Protein Kinases (EC 2.7.11.12) ; Guanylate Cyclase (EC 4.6.1.2) ; Cyclic GMP (H2D2X058MU) ; Calcium Chloride (M4I0D6VV5M) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2000
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/0-306-46838-7_52
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Article: Stabilization of calcium uptake in rat rod outer segments by taurine and ATP.

Militante, J D / Lombardini, J B

Amino acids

2000 Volume 19, Issue 3-4, Page(s) 561–570

Abstract: Calcium ion (Ca2+) uptake was measured in rod outer segments (ROS) isolated from rat retina in the presence of varying concentrations of CaCl2 in the incubation buffer (1.0-2.5 mM). It is known that taurine increases Ca2+ uptake in rat ROS in the ... ...

Abstract	Calcium ion (Ca2+) uptake was measured in rod outer segments (ROS) isolated from rat retina in the presence of varying concentrations of CaCl2 in the incubation buffer (1.0-2.5 mM). It is known that taurine increases Ca2+ uptake in rat ROS in the presence of ATP and at low concentrations of CaCl2 (Lombardini, 1985a); taurine produces no significant effects when CaCl2 concentrations are increased to 1.0 and 2.5mM. With the removal of both taurine and ATP, Ca2+ uptake in rat ROS increased significantly in the presence of 2.5mM CaCl2. Taurine treatment in the absence of ATP was effective in decreasing Ca2+ uptake at the higher levels of CaCl2 (2.0 and 2.5 mM). Similar effects were observed with ATP treatment. The data suggest that taurine and ATP, alone or in combination, limit the capacity of the rat ROS to take up Ca2+ to the extent that a stable uptake level is achieved under conditions of increasing extracellular Ca2+, indicating a protective role for both agents against calcium toxicity.
MeSH term(s)	Adenosine Triphosphate/pharmacology ; Animals ; Calcium/metabolism ; Calcium Chloride/pharmacology ; Ion Transport/drug effects ; Rats ; Rats, Sprague-Dawley ; Rod Cell Outer Segment/metabolism ; Taurine/pharmacology
Chemical Substances	Taurine (1EQV5MLY3D) ; Adenosine Triphosphate (8L70Q75FXE) ; Calcium Chloride (M4I0D6VV5M) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2000-07-07
Publishing country	Austria
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1121341-3
ISSN	1438-2199 ; 0939-4451
ISSN (online)	1438-2199
ISSN	0939-4451
DOI	10.1007/s007260070006
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Article: Stimulatory effect of taurine on calcium ion uptake in rod outer segments of the rat retina is independent of taurine uptake.

Militante, J D / Lombardini, J B

The Journal of pharmacology and experimental therapeutics

1999 Volume 291, Issue 1, Page(s) 383–389

Abstract: ... sulfonamide (J-8) were studied on Ca(2+) and taurine uptake in the rat ROS. Pretreatment of the ROS ... preparation with TFP and J-8 for 5 min before measurement of Ca(2+)-uptake activity produced inhibition ... of the effects of taurine on ATP-dependent Ca(2+) uptake. Both TFP and J-8 also were effective in inhibiting high ...

Abstract	Taurine stimulates ATP-dependent Ca(2+) uptake in the rat rod outer segments (ROS). This stimulation has been linked to the function of the cyclic nucleotide-gated cation channel, implying an important physiologic role for taurine in visual signal transduction. Calmodulin (CaM) has been reported to affect taurine transport in the choroid plexus and also to inhibit the cyclic nucleotide-gated channel; thus, the effects of the competitive CaM inhibitors trifluoperazine (TFP) and N-(8-aminooctyl)-5-iodonaphthalene-1-sulfonamide (J-8) were studied on Ca(2+) and taurine uptake in the rat ROS. Pretreatment of the ROS preparation with TFP and J-8 for 5 min before measurement of Ca(2+)-uptake activity produced inhibition of the effects of taurine on ATP-dependent Ca(2+) uptake. Both TFP and J-8 also were effective in inhibiting high-affinity taurine uptake. In both uptake systems, inhibition by TFP was noncompetitive. These data initially suggested that the stimulatory effects of taurine on ATP-dependent Ca(2+) uptake are dependent on taurine uptake. However, competitive inhibition of taurine uptake by guanidinoethane sulfonate did not produce any effect on the stimulatory effects of taurine. Previous studies have proposed that taurine binds directly to the plasma membrane, and our study demonstrated that TFP inhibits taurine binding to the ROS. In addition, our study demonstrated that taurine uptake is unaffected by varying the concentration of Ca(2+) and that the effects of TFP are independent of Ca(2+), suggesting that TFP acts through a CaM-independent mechanism.
MeSH term(s)	Adenosine Triphosphate/metabolism ; Analysis of Variance ; Animals ; Binding Sites ; Biological Transport/drug effects ; Calcium/metabolism ; Calmodulin/antagonists & inhibitors ; Dopamine Antagonists/pharmacology ; In Vitro Techniques ; Ion Transport/drug effects ; Rats ; Rats, Sprague-Dawley ; Rod Cell Outer Segment/drug effects ; Rod Cell Outer Segment/metabolism ; Taurine/pharmacokinetics ; Taurine/pharmacology ; Trifluoperazine/pharmacology
Chemical Substances	Calmodulin ; Dopamine Antagonists ; Taurine (1EQV5MLY3D) ; Trifluoperazine (214IZI85K3) ; Adenosine Triphosphate (8L70Q75FXE) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	1999-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3106-9
ISSN	1521-0103 ; 0022-3565
ISSN (online)	1521-0103
ISSN	0022-3565
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Article: Taurine uptake activity in the rat retina: protein kinase C-independent inhibition by chelerythrine.

Militante, J D / Lombardini, J B

Brain research

1999 Volume 818, Issue 2, Page(s) 368–374

Abstract: Taurine, a regulatory amino acid of various biochemical processes in the retina, requires an efficient uptake system to maintain the high physiological concentration of taurine in the retina. Taurine uptake was characterized in both whole retinal ... ...

Abstract	Taurine, a regulatory amino acid of various biochemical processes in the retina, requires an efficient uptake system to maintain the high physiological concentration of taurine in the retina. Taurine uptake was characterized in both whole retinal preparations and in isolated rod outer segments (ROS) in terms of uptake kinetics and possible protein kinase C (PKC)-dependent regulation. Two uptake systems, a high- and a low-affinity system, were found in whole retinal preparations while only the high-affinity system was found in the isolated ROS. All the uptake systems characterized were inhibited by guanidinoethane sulfonate (GES), a well-known competitive inhibitor of taurine uptake. Stimulation and inhibition of PKC activity with phorbol myristate acetate and with staurosporine, respectively, produced no significant effect on taurine uptake. On the other hand, chelerythrine (CHT), a documented potent PKC inhibitor, was found to cause significant inhibition of the two taurine uptake systems, presumably through a PKC-independent mechanism. The data demonstrate that CHT may be a useful tool in studying taurine uptake in the retina and specifically in the ROS.
MeSH term(s)	Alkaloids ; Animals ; Benzophenanthridines ; Enzyme Activation ; Enzyme Inhibitors/pharmacology ; In Vitro Techniques ; Phenanthridines/pharmacology ; Protein Kinase C/antagonists & inhibitors ; Rats ; Rats, Sprague-Dawley ; Retina/drug effects ; Retina/metabolism ; Rod Cell Outer Segment/drug effects ; Rod Cell Outer Segment/metabolism ; Taurine/metabolism ; Tetradecanoylphorbol Acetate/pharmacology
Chemical Substances	Alkaloids ; Benzophenanthridines ; Enzyme Inhibitors ; Phenanthridines ; Taurine (1EQV5MLY3D) ; chelerythrine (E3B045W6X0) ; Protein Kinase C (EC 2.7.11.13) ; Tetradecanoylphorbol Acetate (NI40JAQ945)
Language	English
Publishing date	1999-02-13
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/s0006-8993(98)01318-3
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Article: Unique pharmacological interactions of taurine and chelerythrine in the retina.

Militante, J D / Lombardini, J B

Advances in experimental medicine and biology

1998 Volume 442, Page(s) 431–439

Abstract: The effects of taurine and chelerythrine (CHT) on ATP-dependent calcium uptake and the phosphorylation of the approximately 20 kDa phosphoprotein in the retina were compared. In the absence of the CHT, taurine stimulated ATP-dependent calcium uptake and ... ...

Abstract	The effects of taurine and chelerythrine (CHT) on ATP-dependent calcium uptake and the phosphorylation of the approximately 20 kDa phosphoprotein in the retina were compared. In the absence of the CHT, taurine stimulated ATP-dependent calcium uptake and attenuated the phosphorylation of the approximately 20 kDa phosphoprotein. On the other hand, CHT produced the opposite results in the absence of taurine. When the two agents were used simultaneously, it was found that CHT non-competitively inhibited the action of taurine to stimulate calcium uptake, while taurine non-competitively inhibited the action of CHT to stimulate the phosphorylation of the approximately 20 kDa phosphoprotein. The data present an unusual pharmacological mechanism for controlling the signal transduction pathway involving the two distinct cellular processes being studied. Given the unique data, a control system is proposed in which the function of the approximately 20 kDa phosphoprotein is linked to the stimulation of ATP-dependent calcium uptake.
MeSH term(s)	Adenosine Triphosphatases/metabolism ; Alkaloids ; Animals ; Benzophenanthridines ; Calcium/metabolism ; Drug Antagonism ; Enzyme Inhibitors/pharmacology ; Phenanthridines/pharmacology ; Phosphoproteins/metabolism ; Phosphorylation ; Protein Kinase C/antagonists & inhibitors ; Rats ; Rats, Wistar ; Retina/drug effects ; Retina/metabolism ; Taurine/pharmacology
Chemical Substances	Alkaloids ; Benzophenanthridines ; Enzyme Inhibitors ; Phenanthridines ; Phosphoproteins ; Taurine (1EQV5MLY3D) ; chelerythrine (E3B045W6X0) ; Protein Kinase C (EC 2.7.11.13) ; Adenosine Triphosphatases (EC 3.6.1.-) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	1998
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-1-4899-0117-0_53
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Article: Pharmacological characterization of the effects of taurine on calcium uptake in the rat retina.

Militante, J D / Lombardini, J B

Amino acids

1998 Volume 15, Issue 1-2, Page(s) 99–108

Abstract: Taurine is known to increase ATP-dependent calcium ion (Ca2+) uptake in retinal membrane preparations and in isolated rod outer segments (ROS) under low calcium conditions (10 microM) (Pasantes-Morales and Ordóñez, 1982; Lombardini, 1991). In this report, ...

Abstract	Taurine is known to increase ATP-dependent calcium ion (Ca2+) uptake in retinal membrane preparations and in isolated rod outer segments (ROS) under low calcium conditions (10 microM) (Pasantes-Morales and Ordóñez, 1982; Lombardini, 1991). In this report, ATP-dependent Ca2+ uptake in retinal membrane preparations was found to be inhibited by 5 microM cadmium (Cd2+), suggesting the involvement of cation channel activation. The activation of cGMP-gated cation channels, which are found in the ROS, is a crucial step in the phototransduction process. An inhibitor of cGMP-gated channels, LY83583, was found to inhibit taurine-stimulated ATP-dependent Ca2+ uptake but had no effect on ATP-dependent Ca2+ uptake in the absence of taurine, indicating that taurine may be increasing ATP-dependent Ca2+ uptake through a mechanism of action involving the opening of cGMP-gated channels. The activation of cGMP-gated channels with dibutyryl-cGMP and with phosphodiesterase inhibition using zaprinast caused an increase in ATP-dependent Ca2+ uptake in isolated ROS, but not in taurine-stimulated ATP-dependent Ca2+ uptake. LY83583 had the same effects in isolated ROS as in retinal membrane preparations. Another inhibitor of cGMP-gated channels, Rp-8-Br-PET-cGMPS, produced the same pattern of inhibition in isolated ROS as LY83583. Thus, there appears to be a causal link between taurine and the activation of the cGMP-gated channels in the ROS under conditions of low calcium concentration, a connection that suggests an important role for taurine in the visual signalling function of the retina.
MeSH term(s)	Adenosine Triphosphate/metabolism ; Aminoquinolines/pharmacology ; Animals ; Biological Transport/drug effects ; Cadmium/pharmacology ; Calcium/metabolism ; Calcium Channels/drug effects ; Cyclic GMP/metabolism ; Dose-Response Relationship, Drug ; Ion Channel Gating ; Rats ; Rats, Wistar ; Rod Cell Outer Segment/metabolism ; Taurine/pharmacology
Chemical Substances	Aminoquinolines ; Calcium Channels ; Cadmium (00BH33GNGH) ; Taurine (1EQV5MLY3D) ; Adenosine Triphosphate (8L70Q75FXE) ; 6-anilino-5,8-quinolinedione (91300-60-6) ; Cyclic GMP (H2D2X058MU) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	1998
Publishing country	Austria
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1121341-3
ISSN	1438-2199 ; 0939-4451
ISSN (online)	1438-2199
ISSN	0939-4451
DOI	10.1007/bf01345283
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Article: Effect of taurine on chelerythrine inhibition of calcium uptake and ATPase activity in the rat retina.

Militante, J D / Lombardini, J B

Biochemical pharmacology

1998 Volume 55, Issue 5, Page(s) 557–565

Abstract: Taurine potentiates calcium uptake in whole retinal homogenates as well as in rod outer segments and mitochondrial fractions. The aim of this study was to correlate taurine potentiation of calcium uptake with its effects on other cellular processes ... ...

Abstract	Taurine potentiates calcium uptake in whole retinal homogenates as well as in rod outer segments and mitochondrial fractions. The aim of this study was to correlate taurine potentiation of calcium uptake with its effects on other cellular processes through the use of chelerythrine (CHT), a modulator of protein kinase C (PKC), ATPase activity, and, as recently shown, of retinal protein phosphorylation. CHT inhibited calcium uptake only when ATP was present, and inhibition increased significantly in conditions of ATP excess. Taurine potentiated ATP-dependent calcium uptake but decreased the potency of ATP to induce uptake activity. CHT inhibition of calcium uptake exhibited similar potencies in the presence and absence of taurine, and this inhibition seemed to be independent of PKC inhibition. Because of the ATP-dependence of the observed effect, total ATPase activity was studied using similar treatments. In the absence of taurine, CHT inhibited ATPase activity with the same potency (IC50 approximately 59.3 microM) as with calcium uptake inhibition (IC50 approximately 87.9 microM), presenting a possible mechanism of action of CHT. In the presence of taurine, no such correlation was observed, suggesting an ATPase-independent mechanism of action. In fact, taurine did not potentiate ATPase activity, but rather it decreased the potency of CHT inhibition of ATPase, effects incongruent with the effects of taurine on calcium uptake and on CHT inhibition of calcium uptake. Enzyme kinetic experiments provided more supporting data. Taurine was found to cause an increase in the affinity of the ATP substrate for the ATPase enzyme, contradicting the aforementioned effect of taurine to decrease the potency of ATP to induce calcium uptake. Thus, taurine seems to increase calcium uptake through a hitherto unreported mechanism distinct from its modulation of ATPase activity.
MeSH term(s)	Adenosine Triphosphatases/antagonists & inhibitors ; Alkaloids ; Animals ; Benzophenanthridines ; Calcium/antagonists & inhibitors ; Calcium/metabolism ; Enzyme Inhibitors/pharmacology ; Kinetics ; Phenanthridines/pharmacology ; Phosphorylation ; Protein Kinase C/antagonists & inhibitors ; Rats ; Rats, Wistar ; Retina/drug effects ; Retina/enzymology ; Retina/metabolism ; Taurine/pharmacology
Chemical Substances	Alkaloids ; Benzophenanthridines ; Enzyme Inhibitors ; Phenanthridines ; Taurine (1EQV5MLY3D) ; chelerythrine (E3B045W6X0) ; Protein Kinase C (EC 2.7.11.13) ; Adenosine Triphosphatases (EC 3.6.1.-) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	1998-03-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/s0006-2952(97)00502-9
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