- Email: [email protected]
Effect of taurine on arterial, uterine and cardiac PGI2 and TXA2 synthesis in the rat
PROSTAGLANDINS
EFFECT OF TAURINE ON ARTERIAL, UTERINE AND CARDIAC PGIa and TXA, SYNTHESIS IN THE RAT. K.E.H. El Tahir, A.M. Ageel and A.R. Abu-Jayyab Department of Pharmacology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh-11451 Kingdom of Saudi Arabia. ABSTRACT: The influence of taurine (in drinking water for 6 weeks) on PG12 and TXA, synthesis by some female rat organs was investigated using radioimmunoassayand platelet antiaggregatorybioassay. Taurine 100 and 200 mg/kg/day increased aortic PGIz release from 0.59 i 0.04 (control) to 0.85 + 0.05 and 1.01 + 0.06 ng/mg, respectively and that by the myometrium from 0.24 + 0.02 (control) to 0.38+0.01 and 0.50 ?r0.04 ng/mg wet tissue, respectively (PLU.05, n = 6). It did not affect PGIz and TXA2 production in the heart or TXAz in the aorta. Taurine 200 mg/kg depressed uterine TXA, synthesis from 148.6 i 9.8 (control) to 85.4 + 6.8 pg/mg (PCO.05, n = 6). Furthermore taurine 0.4 and 0.8 mu in vitro stimulated PG12 release by the myometrial and aortic tissues from pregnant rats. The stimulant effect of taurine on PtiI*may be related to its antioxidant effect whereas its inhibitory effect on uterine TXA, may result from direction of synthesis towards PGI,. It is concluded that endogenous taurine may participate in regulation of PGs synthesis and that prostanoids may contribute to its known actions. On broad basis, taurine-induced release of PGI, may prove of potential value in those ailments characterised by deficiency in PtiIprelease. INTRODUCTION: The S-containing amino acid taurine is detected in high concentrations in the brain, heart, uterus and some other peripheral organs (1, 2, 3). It is believed to participate in regulation of Ca' iOnS movement across membranes (4). It affects CAMP level within some organs (S), relaxes arteries (6) and decreases arterial blood pressure in some mammals (7). Furthermore, its precursor, glutathione, affects PGs synthesis in some organs (8). These observations and many others prompted us to investigate the influence of taurine on PGI, and TXA2 synthesis in some rat organs. METHODS: Female Wistar rats (170g) were divided into 4 groups [n = 6/ group). One group served as a control and the other 3 administered taurine 50, 100 or 200 mg/kg/day in the drinking water for 6 weeks. All rats were killed on day of proestrous, the hearts, thoracic aortae and uteri were removed and immersed in ice-cold Krebs' solution (K.S) of the following composition (til):
JANUARY
1987 VOL.
33 NO. 1
17
PROSTAGLANDINS
Na+ 137.4, K+ 5.9, 1.2, glucose 11.
Ca
z+
2.5,
z+ Mg 1.2,
Cl- 134,
HCUs- 15.5,
H,Pc4
blotted ‘The tissues were cut longitudinally, washed in K.S. dry and known weights (40-150mgJ were placed in small glass beakers. 2 ml K.S. were added, the tissues chopped with a scissor incubated at 37’C for 30 min, acidified to pH 3.5 with 5% aqueous citric acid The ethereal and extracted twice with 2 volumes of diethyl ether. extracts were dried over anhydrous Na,S04 and evaporated under Nz Each residue was dissolved in 100 ~1 of the eluting solvent gas. (see below) and applied to a silica gel mini column (12 x 0.5 cm). TXB, and 6-oxo-PGFl&were eluted using the organic layer of a mixture of ethylacetate : isoctane : acetic acid : water (110 : 50 : 25 : 100 Fractions containing TXB2 and 6-oxo-PGFl%were identified v/v/v/v). using labeled prostanoids. The fractions were evaporated, dissolved in K.S. and the prostanoids quantitated using Amersham’s radioimmunoassay kits that utilize a high specific activity TXB, or 6-0x0PGFl&l251-iodotyrosine methyl ester tracers. PGI, release by myometrial tissues of treated rats was determined by platelet aggregation bioassay using rat platelets and adenosine diphosphate (ADP) Myometrial tissue from one horn of each as an aggregating agent. of the treated rats was prepared and incubated in K.S. for 3 min at 37°C in an aggregometer chamber as described previously (9,lOJ. 20 pl aliquots were then removed and assayed for PGIz-like activity against standard PGIz. ln some experiments aortic and myometrial tissues from nontreated 18-day pregnant rats were similarly prepared and incubated in presence of taurine 0.4 and 0.8 mM for 30 min at 37OC, chopped, incubated for 3 min at 37OC and PG12 release was To cater for any effect of the quantitated by bioassay as above. carried-over taurine in the tested aliquots, appropriate controls were instituted. Prostanoids 1 release is reported as ng or pg/mg wet tissue. Statistical significance was calculated using Student’s ‘t’ test for paired or unpaired samples as appropriate. Chemicals used were: taurine (Fluka), (Wellcome), ADP (Boehringer) , slicagel
labeled PGs (Amersham), PG12 (Fluka) and other chemicals
(BDHJ .
RESULTS: AJ
Effect
of taurine
in vivo:
Chronic treatment of rats with taurine in drinking water did not effect water consumption in any of the treated groups compared with the control group (in all groups the average was 145-150 ml water/group). Chronic treatment of rats with taurine 50, 100 or 200 mg/kg stimulated aortic PGI, release (as indicated by increases in its metabolite 6-0x0-PGFl* ) in a dose-dependent manner. Significant stimulations were observed at 100 and 200 mg/kg (P(O.05, n = 6).
18
JANUARY
1987 VOL.
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PROSTAGLANDINS
Taurine did not affect PG12 synthesis in the heart or TXA, (as indicated by its metabolite TXBa) in both organs. However, It significantly decreased TXAa in whole uterine tissue from 148.6 + 9.8 (control) to 128.2 ? 7.8, 92.9 ? 8.1 and 85.4 + 6.8 pg/mg wet tissue after treatment with 50, 100 and 200 mg taurine/kg, respectively. The decreases induced by 100 and 200 mg taurine/kg were significant (PLO.05, n = 6). The cumulative findings for the influence of taurine on PGI, and TXA, (measured as their respective metabolites) release by the aorta and the heart is shown in Table 1. Table 1.
Influence of taurine on 6-oxo-PGF and TXBz in rat heart and aorta (pg/mg wet tissuej':
Tissue/ Prostanoid
Control
50
Taurine mg/kg/day 200 100
Aorta 6-oxo-PGFlo< TXBz
597?45 84.6+4
610 f 50
853 + 35*
1013 f 65"
85.7 f 7.6
72.8 + 8.1
90.8 + 7.8
20 + 3
24 ? 2
22 ? 3
18.8 + 1.8
17.3 ? 1.6
Heart 6-oxo-PtiFly TXB:!
20+2 16.521.5
18.0 2 2
* PLU.05, n = 6 (comparedwith control). The influence of chronic taurine treatment on myometrial PGI, release as revealed by the platelet antiaggregatoryassay is shown in Figure 1. Addition of ADP (10 TM) to rat platelets rich plasma induced complete aggregation. Addition of aliquots of incubation media 1 min before ADP inhibited ADP-induced aggregation. For instance, a 20 pl control aliquot contained an antiaggregatoryactivity equivalent to 2.5 ng PtiI*. Equivalent aliquots from tissue of animals treated with taurine 50, 100 and 200 mg/kg contained 3, 5.8 and 7.8 ng PGIa, respectively. The mean PG12 production by control tissues was 0.24 ? 0.02 ng/mg. This was increased to 0.26 2 0.02, U.38 ?r0.01 and 0.50 lr0.04 ng/mg by treatment with 50, 100 and 200 mg taurine/kg, respectively. The increases induced by taurine 100 and 200 mg/kg were significantlydifferent from control (P
W
Effect of taurine on PtiI,release in vitro:
Pretreatment of aortic tissue from pregnant rats with taurine 0.4 and 0.8 mM increased PGI, release from 1.5 + 0.2 (control) to
JANUARY
1987 VOL. 33 NO. 1
19
PROSTAGLANDINS
l
2.5ng 6
20 Td
1
5,w 2
l
l
l
l
l
2Oyl 7100
2Opl T200
long I,
Figure 1. The effect of chronic treatment with taurine on rat myometrial PGI, release. The change in light transmission caused by addition of ADP 10 ti (e) to rat titrated platelet rich plasma was recorded. Addition of ADP alone caused irreversibleplatelet aggregation. Addition of 20 ul aliquot of control incubation medium (C) one min before ADP decreased ADP-induced platelet aggregation due to the released PGI,. Equivalent aliquots from tissue obtained from rats treated with taurine 50, 100 and 200 mg/kg/day for 6 weeks (T50, TlOO, T200, respectively) contained higher concentrationsof PGI, in a dose dependent manner.
20
JANUARY
1987 VOL. 33 NO. 1
PROSTAGLANDINS
1.80 + 0.20 and 2.70 f 0.25 ng/mg, respectively. Similarly the above two doses of taurine increased myometrial PGIz release from 2.1 + 0.15 (control) to 2.5 + 0.02 and 3.60 + 0.27 ng/mg, respectively. The effect of taurine 0.4 and 0.8 mM on PGIz release by aortic and myometrial tissue from 18-day pregnant rats is shown in Table 2. As shown in the Table, taurine (0.8 mM) significantly increased PGIz release in both organs (PLO.05, n = 5). Table 2.
Effect of taurine on PGI, release by pregnant rat aorta and myometrium in vitro. ( ng/mg wet weight tissue).
0.4
Taurine (mM) 0.8
Tissue
Control
Aorta
1.5 + 0.2
1.8 + 0.2
2.7 ?:0.25*
Myometrium
2.1 ? 0.15
2.5 2 0.2
3.6 5 0.27"
* PL.O.05, n = 5 (comparedwith the respective control). DISCUSSION: Treatment of rats with taurine or incubation of rat organs with taurine in vitro, stimulated PGIz synthesis in the aortic and myometrial tissues without affecting the production in the heart. The synthesis of TXAz in either the heart or the aorta was not affected. The differential effect on prostanoid synthesis in the arota suggests that the site of action of taurine may be distal to the formation of PGHz,the precursor of the two prostanoids. A likely site is the enzyme PGIz synthetase. Taurine may protect the enzyme from the deleterious effect of lipid peroxides (11). Indeed, taurine is reported to inhibit lipid peroxidation in some tissues (12). The inability of taurine to affect PGs synthesis is the heart may be due to the low activity of the synthesising enzymes in this organ as revealed by the low production of the prostanoids. Taurine stimulated PGI, release in the myometrium and inhibited TXAz synthesis in the whole uterus. The characterizationof the myometrial antiaggregatoryactivity as PGI2 has been previously discussed (9, 10). The stimulant effect of taurine on myometrial PGI, may also involve protection of the enzyme from lipid peroxides whereas the inhibitory effect on TXAz may be a consequence of competition between an activated PGIz synthetase with TXAz synthetase to a limited quantity of PGH,. However, direct inhibition of TXAz synthetase cannot be ruled out. The stimulant effect of taurine on the potent vasodilatant PGIz
JANUARY
1987 VOL. 33 NO. 1
21
PROSTAGLANDINS
may contribute to some of the previously reported actions of taurine such as relaxation of arteries (6)and reduction of arterial blood pressure (7, 13). In addition the low synthesis of PGIz by arterial tissues of diabetic animals (14) may be related to the low plasma taurine levels observed in diabetes (15). Uterine fluid taurine has been shown to be elevated following fertilizationand/or at ovum implantation in some mammals (3, 16). The latter period is also characterizedby temporal variations in PGIz production (17). On the light of the stimulant effect of taurine on myometrial PGIz synthesis, it is tempting to suggest the participation of taurine in regulation of uterine PGIz synthesis. Such a role may be strengthenedby the parallelism between uterine taurine and PGI, under the influence of steroidal hormones (16,18,19). z+. TXAz is reported to enhance release of intracellularCa ions whereas PGIz interferes with such release (20). Based on thezpresent findings the previously reported effect of taurine on free Ca + ions availability (41, may reside in part on the ability of taurine to influence PGs synthesis in some tissues. In conclusion, the ability of taurine to affect PGIz and TXAz synthesis, suggests that it may act as an endogenous regulator for PGs synthesis. On broad basis, taurine-inducedrelease of PGlz may prove of potential value in those ailments characterizedby deficiency in PGI, release. REFEKENCES: 1.
Hudson, U.B., A.Vernadakis and P.S. Timiras. Regional changes in aminoacid concentration in the developing brain and the effects of neonatal administrationof estradiol. Brain Res. -23: 213. 1970.
2.
Matsuda, T., S. Yamagami, T. Mizui, A. Baba and H. Iwata. Increase of cardiac taurine by glucocorticoids. Biochem. Pharmacol.-27: 2973. 1978.
3.
Jaszczak, S. and E.S.E. Hafez. Free amino acids in uterine and blastocoelic fluids in the rabbit as affected by ovarian steroids. Int. J. Fert. -17: 191. 1973.
4.
Huxtable, K. and R. Bressler. Effect of taurine on a muscle intracellularmembrane. Biochim. Biophys. Acta 323: 573. 1973.
5.
Mal'chikova, L.S. and E.P. Elizarova. Taurine and CAMP content in the heart. Kardiologiya-21: 85. 1981.
6.
Franconi, F., A. tiiotti,S. Manzini, F. Martini, I. Stendardi and L. Zelletti. Observations on the action of taurine at arterial and cardiac level. Adv. Exp. Med. Biol. 139: 181.1982
22
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1987 VOL. 33 NO. I
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7.
Stanton, H.C. and F.H. Woodhouse. Effect of%-aminobutyric acid and some related compounds on the cardiovascularsystem of anaesthetizeddogs. J. Pharmacol. Exp. Ther. -128: 233.1960.
8.
Tai, H.H., C.L. Tai and C.S. Hollander. Biosynthesis of prostaglandins in rabbit kindey medulla. Biochem. J. 154: 257.1976.
9.
El Tahir, K.E.H. and K.I. Williams. Factors affecting prostacyclin formation by the rat pregnant myometrium. Br. J. Pharmac. -71: 641. 1980.
10.
Ageel, A.M., K.E.H. El Tahir and A.R. Abu-Jayyab. Effect of bromocriptine on prostacyclin release and cyclic nucleotides on rat aortic and uterine tissues. Prostaglandins-30: 369. 1985.
11.
Salmon, J.A., D.R. Smith, R.J. Flower, S. Moncada and J.R. Vane. Further studies in theenzymic conversion of PG endoperoxide into PGIz by porcine aorta microsomes. Biochem. Biophys. Acta. 523: 250. 1978.
12.
Alvarez, J.G. and B.T. Storey. Taurine, hypotaurine, epinephrine and albumin inhibit lipid peroxidation in rabbit spermatozoa and protect against loss of motility. Biol. Keprod. -29: 548. 1983.
13.
Uzaki, M., M. Niwa, L. J. Wei, H. Tsuchiyama, K. Mawatari and K. Yamashiro. Effect of taurine on blood pressure and fat metabolism in experimental hypertension. Ganryu Aminosan -3: 115. 1980.
14.
El Tahir, K.E.H., K.I. Williams, D.J. Betteridge and J.P.D. Reckless. Diffe'ential prostacyclin production by tissue from pregnant diabetic rats. Clin. Sci. 60: 9p. 1981.
15.
Kawashima, S. Metabolism of amino acids in diabetic patients. I. Fasting plasma free amino acids. Tohoku Igaku Zasshi -8U: 171. 1969.
16.
Hafez, E.S.E. and S. Jaszczak. Gradient concentrationof amino acids in the uterine and blastocoelic fluids in the rabbit as affected by ovarian hormones. In: Fertility and Sterility Proceedings. World Congress 7th (T. Hasegawa, M. Hayashi and F.G. Etling, eds). Excerpta Med., Amsterdam, p.738, 1973.
17.
Williams K.I. and K.E.H. El Tahir. Spatial and temporal variations in prostacyclin production by rat pregnant uterus. Adv. ProstaglandinsThrombox. Res. -8: 1413. 1980.
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18.
Lorincz, A.B., R.E. Kuttner and R.P. Searles. Free amino acids in human female reproductive tissues. Nebraska State Med. J. -50: 320. 1965.
19. tiimeno.M.F., Borda, E.S., M.E. Lazzari and A.L. Gimeno. Ovarian hormones inhibit the release of prostacyclin-like material from isolated rat uterus. Prostaglandins-20: 223. 1980. 20. Horrobin, D.F., M.S. Manku, S. Cunnane, M. Karmazyn, R.O. Morgan, A.I. Ally and R.A. Karmali. Regulation of cytoplasmic calcium. Interactionsbetween prostaglandins,prostacyclin, thromboxane AZ, zinc, copper and taurine. Can. J. Neurol. Sci. -5: 93. 1978.
Editor:
24
1i.R.
Behrman
Received:
S-30-86
JANUARY
Accepted:
1987 VOL. 33 NO. 1
11-11-86
EFFECT OF TAURINE ON ARTERIAL, UTERINE AND CARDIAC PGIa and TXA, SYNTHESIS IN THE RAT. K.E.H. El Tahir, A.M. Ageel and A.R. Abu-Jayyab Department of Pharmacology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh-11451 Kingdom of Saudi Arabia. ABSTRACT: The influence of taurine (in drinking water for 6 weeks) on PG12 and TXA, synthesis by some female rat organs was investigated using radioimmunoassayand platelet antiaggregatorybioassay. Taurine 100 and 200 mg/kg/day increased aortic PGIz release from 0.59 i 0.04 (control) to 0.85 + 0.05 and 1.01 + 0.06 ng/mg, respectively and that by the myometrium from 0.24 + 0.02 (control) to 0.38+0.01 and 0.50 ?r0.04 ng/mg wet tissue, respectively (PLU.05, n = 6). It did not affect PGIz and TXA2 production in the heart or TXAz in the aorta. Taurine 200 mg/kg depressed uterine TXA, synthesis from 148.6 i 9.8 (control) to 85.4 + 6.8 pg/mg (PCO.05, n = 6). Furthermore taurine 0.4 and 0.8 mu in vitro stimulated PG12 release by the myometrial and aortic tissues from pregnant rats. The stimulant effect of taurine on PtiI*may be related to its antioxidant effect whereas its inhibitory effect on uterine TXA, may result from direction of synthesis towards PGI,. It is concluded that endogenous taurine may participate in regulation of PGs synthesis and that prostanoids may contribute to its known actions. On broad basis, taurine-induced release of PGI, may prove of potential value in those ailments characterised by deficiency in PtiIprelease. INTRODUCTION: The S-containing amino acid taurine is detected in high concentrations in the brain, heart, uterus and some other peripheral organs (1, 2, 3). It is believed to participate in regulation of Ca' iOnS movement across membranes (4). It affects CAMP level within some organs (S), relaxes arteries (6) and decreases arterial blood pressure in some mammals (7). Furthermore, its precursor, glutathione, affects PGs synthesis in some organs (8). These observations and many others prompted us to investigate the influence of taurine on PGI, and TXA2 synthesis in some rat organs. METHODS: Female Wistar rats (170g) were divided into 4 groups [n = 6/ group). One group served as a control and the other 3 administered taurine 50, 100 or 200 mg/kg/day in the drinking water for 6 weeks. All rats were killed on day of proestrous, the hearts, thoracic aortae and uteri were removed and immersed in ice-cold Krebs' solution (K.S) of the following composition (til):
JANUARY
1987 VOL.
33 NO. 1
17
PROSTAGLANDINS
Na+ 137.4, K+ 5.9, 1.2, glucose 11.
Ca
z+
2.5,
z+ Mg 1.2,
Cl- 134,
HCUs- 15.5,
H,Pc4
blotted ‘The tissues were cut longitudinally, washed in K.S. dry and known weights (40-150mgJ were placed in small glass beakers. 2 ml K.S. were added, the tissues chopped with a scissor incubated at 37’C for 30 min, acidified to pH 3.5 with 5% aqueous citric acid The ethereal and extracted twice with 2 volumes of diethyl ether. extracts were dried over anhydrous Na,S04 and evaporated under Nz Each residue was dissolved in 100 ~1 of the eluting solvent gas. (see below) and applied to a silica gel mini column (12 x 0.5 cm). TXB, and 6-oxo-PGFl&were eluted using the organic layer of a mixture of ethylacetate : isoctane : acetic acid : water (110 : 50 : 25 : 100 Fractions containing TXB2 and 6-oxo-PGFl%were identified v/v/v/v). using labeled prostanoids. The fractions were evaporated, dissolved in K.S. and the prostanoids quantitated using Amersham’s radioimmunoassay kits that utilize a high specific activity TXB, or 6-0x0PGFl&l251-iodotyrosine methyl ester tracers. PGI, release by myometrial tissues of treated rats was determined by platelet aggregation bioassay using rat platelets and adenosine diphosphate (ADP) Myometrial tissue from one horn of each as an aggregating agent. of the treated rats was prepared and incubated in K.S. for 3 min at 37°C in an aggregometer chamber as described previously (9,lOJ. 20 pl aliquots were then removed and assayed for PGIz-like activity against standard PGIz. ln some experiments aortic and myometrial tissues from nontreated 18-day pregnant rats were similarly prepared and incubated in presence of taurine 0.4 and 0.8 mM for 30 min at 37OC, chopped, incubated for 3 min at 37OC and PG12 release was To cater for any effect of the quantitated by bioassay as above. carried-over taurine in the tested aliquots, appropriate controls were instituted. Prostanoids 1 release is reported as ng or pg/mg wet tissue. Statistical significance was calculated using Student’s ‘t’ test for paired or unpaired samples as appropriate. Chemicals used were: taurine (Fluka), (Wellcome), ADP (Boehringer) , slicagel
labeled PGs (Amersham), PG12 (Fluka) and other chemicals
(BDHJ .
RESULTS: AJ
Effect
of taurine
in vivo:
Chronic treatment of rats with taurine in drinking water did not effect water consumption in any of the treated groups compared with the control group (in all groups the average was 145-150 ml water/group). Chronic treatment of rats with taurine 50, 100 or 200 mg/kg stimulated aortic PGI, release (as indicated by increases in its metabolite 6-0x0-PGFl* ) in a dose-dependent manner. Significant stimulations were observed at 100 and 200 mg/kg (P(O.05, n = 6).
18
JANUARY
1987 VOL.
33 NO. 1
PROSTAGLANDINS
Taurine did not affect PG12 synthesis in the heart or TXA, (as indicated by its metabolite TXBa) in both organs. However, It significantly decreased TXAa in whole uterine tissue from 148.6 + 9.8 (control) to 128.2 ? 7.8, 92.9 ? 8.1 and 85.4 + 6.8 pg/mg wet tissue after treatment with 50, 100 and 200 mg taurine/kg, respectively. The decreases induced by 100 and 200 mg taurine/kg were significant (PLO.05, n = 6). The cumulative findings for the influence of taurine on PGI, and TXA, (measured as their respective metabolites) release by the aorta and the heart is shown in Table 1. Table 1.
Influence of taurine on 6-oxo-PGF and TXBz in rat heart and aorta (pg/mg wet tissuej':
Tissue/ Prostanoid
Control
50
Taurine mg/kg/day 200 100
Aorta 6-oxo-PGFlo< TXBz
597?45 84.6+4
610 f 50
853 + 35*
1013 f 65"
85.7 f 7.6
72.8 + 8.1
90.8 + 7.8
20 + 3
24 ? 2
22 ? 3
18.8 + 1.8
17.3 ? 1.6
Heart 6-oxo-PtiFly TXB:!
20+2 16.521.5
18.0 2 2
* PLU.05, n = 6 (comparedwith control). The influence of chronic taurine treatment on myometrial PGI, release as revealed by the platelet antiaggregatoryassay is shown in Figure 1. Addition of ADP (10 TM) to rat platelets rich plasma induced complete aggregation. Addition of aliquots of incubation media 1 min before ADP inhibited ADP-induced aggregation. For instance, a 20 pl control aliquot contained an antiaggregatoryactivity equivalent to 2.5 ng PtiI*. Equivalent aliquots from tissue of animals treated with taurine 50, 100 and 200 mg/kg contained 3, 5.8 and 7.8 ng PGIa, respectively. The mean PG12 production by control tissues was 0.24 ? 0.02 ng/mg. This was increased to 0.26 2 0.02, U.38 ?r0.01 and 0.50 lr0.04 ng/mg by treatment with 50, 100 and 200 mg taurine/kg, respectively. The increases induced by taurine 100 and 200 mg/kg were significantlydifferent from control (P
W
Effect of taurine on PtiI,release in vitro:
Pretreatment of aortic tissue from pregnant rats with taurine 0.4 and 0.8 mM increased PGI, release from 1.5 + 0.2 (control) to
JANUARY
1987 VOL. 33 NO. 1
19
PROSTAGLANDINS
l
2.5ng 6
20 Td
1
5,w 2
l
l
l
l
l
2Oyl 7100
2Opl T200
long I,
Figure 1. The effect of chronic treatment with taurine on rat myometrial PGI, release. The change in light transmission caused by addition of ADP 10 ti (e) to rat titrated platelet rich plasma was recorded. Addition of ADP alone caused irreversibleplatelet aggregation. Addition of 20 ul aliquot of control incubation medium (C) one min before ADP decreased ADP-induced platelet aggregation due to the released PGI,. Equivalent aliquots from tissue obtained from rats treated with taurine 50, 100 and 200 mg/kg/day for 6 weeks (T50, TlOO, T200, respectively) contained higher concentrationsof PGI, in a dose dependent manner.
20
JANUARY
1987 VOL. 33 NO. 1
PROSTAGLANDINS
1.80 + 0.20 and 2.70 f 0.25 ng/mg, respectively. Similarly the above two doses of taurine increased myometrial PGIz release from 2.1 + 0.15 (control) to 2.5 + 0.02 and 3.60 + 0.27 ng/mg, respectively. The effect of taurine 0.4 and 0.8 mM on PGIz release by aortic and myometrial tissue from 18-day pregnant rats is shown in Table 2. As shown in the Table, taurine (0.8 mM) significantly increased PGIz release in both organs (PLO.05, n = 5). Table 2.
Effect of taurine on PGI, release by pregnant rat aorta and myometrium in vitro. ( ng/mg wet weight tissue).
0.4
Taurine (mM) 0.8
Tissue
Control
Aorta
1.5 + 0.2
1.8 + 0.2
2.7 ?:0.25*
Myometrium
2.1 ? 0.15
2.5 2 0.2
3.6 5 0.27"
* PL.O.05, n = 5 (comparedwith the respective control). DISCUSSION: Treatment of rats with taurine or incubation of rat organs with taurine in vitro, stimulated PGIz synthesis in the aortic and myometrial tissues without affecting the production in the heart. The synthesis of TXAz in either the heart or the aorta was not affected. The differential effect on prostanoid synthesis in the arota suggests that the site of action of taurine may be distal to the formation of PGHz,the precursor of the two prostanoids. A likely site is the enzyme PGIz synthetase. Taurine may protect the enzyme from the deleterious effect of lipid peroxides (11). Indeed, taurine is reported to inhibit lipid peroxidation in some tissues (12). The inability of taurine to affect PGs synthesis is the heart may be due to the low activity of the synthesising enzymes in this organ as revealed by the low production of the prostanoids. Taurine stimulated PGI, release in the myometrium and inhibited TXAz synthesis in the whole uterus. The characterizationof the myometrial antiaggregatoryactivity as PGI2 has been previously discussed (9, 10). The stimulant effect of taurine on myometrial PGI, may also involve protection of the enzyme from lipid peroxides whereas the inhibitory effect on TXAz may be a consequence of competition between an activated PGIz synthetase with TXAz synthetase to a limited quantity of PGH,. However, direct inhibition of TXAz synthetase cannot be ruled out. The stimulant effect of taurine on the potent vasodilatant PGIz
JANUARY
1987 VOL. 33 NO. 1
21
PROSTAGLANDINS
may contribute to some of the previously reported actions of taurine such as relaxation of arteries (6)and reduction of arterial blood pressure (7, 13). In addition the low synthesis of PGIz by arterial tissues of diabetic animals (14) may be related to the low plasma taurine levels observed in diabetes (15). Uterine fluid taurine has been shown to be elevated following fertilizationand/or at ovum implantation in some mammals (3, 16). The latter period is also characterizedby temporal variations in PGIz production (17). On the light of the stimulant effect of taurine on myometrial PGIz synthesis, it is tempting to suggest the participation of taurine in regulation of uterine PGIz synthesis. Such a role may be strengthenedby the parallelism between uterine taurine and PGI, under the influence of steroidal hormones (16,18,19). z+. TXAz is reported to enhance release of intracellularCa ions whereas PGIz interferes with such release (20). Based on thezpresent findings the previously reported effect of taurine on free Ca + ions availability (41, may reside in part on the ability of taurine to influence PGs synthesis in some tissues. In conclusion, the ability of taurine to affect PGIz and TXAz synthesis, suggests that it may act as an endogenous regulator for PGs synthesis. On broad basis, taurine-inducedrelease of PGlz may prove of potential value in those ailments characterizedby deficiency in PGI, release. REFEKENCES: 1.
Hudson, U.B., A.Vernadakis and P.S. Timiras. Regional changes in aminoacid concentration in the developing brain and the effects of neonatal administrationof estradiol. Brain Res. -23: 213. 1970.
2.
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Editor:
24
1i.R.
Behrman
Received:
S-30-86
JANUARY
Accepted:
1987 VOL. 33 NO. 1
11-11-86