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FFECTSOF PROSTAGLANDINS F2ex: AND El ON THE CONTRACTILlTV OF NON-PREGNANT HUMAN FALLOPIAN TUBE IN VITRO M.T.M. JIFFRY* AND P. VIRUTAMASEN Department of Obstetrics and Gvneecoloqv. Chulalongkorn Hospital, Rama IV Road, Bangkok- Thailand (Received on March 28. 1980) Summary: The effects of PGF 2 ex: and PGE 2 on the distal part of the isolated non-pregnant human fallopian tubes obtained from known menstrual phases has been investigated. Both PGF 2CO and PGE 2 produced an increased contractility of failopian tube. However. PGF 2 cx: was found to be more potent than PGE 2 and also the contractions produced by the former compound showed wave forms of relatively high amplitude and low in frequency than that produced by the latter com- pound. These two compounds did not show a priming effect on each other. There was no dis- cernible effect of phase of the menstrual cycle upon the contractile response to PG. Key words: prostaglandin F 2 ex: and El contractility non-pregnant human tallopian tube INTRODUCTION The excitability produced by prostaglandin F 2 ex: (PGF2ex:) on the myometrial and fallopian tubal musculature was undisputed. in human and animal studies conducted in vivo and in vitro (4.5.11). However. there were contradictory findings on the effect of the PGE serieson the uterine and fallopian tube musculature. Early in vitro studies on non-pregnant human myometrium indicated that PGE series exerted an antagonistic effect to that produced by PGF2ex: (1 2). However. later in vitro studies on pregnant and non-pregnant human myometrium showed increased contractility on exposure to PGE series (3.7.9). A few in vivo studies on both pregnant and non-pregnant human myometrium also showed spasmogenic effects produced by intravenous administration of PGE (6.8). Similarly. in vitro studies conducted on non-pregnant human fallopian tube showed excitatory effects at the proximal region and relaxation at the distal part due to PGE (9). In a later study. the same group demonstrated an increase in motility due to PGE. on the distal part of the non-pregnant human fallopian tube in vitro. However. there were no recent studies done to re-examine the reported contradictory findings on the effect of PGE on the distal part of the non-pregnant human fallopian tube obtained at known phases of the menstrual cycle. Therefore. the present investigation was conducted in vitro, as part of a continuous series of experiments to investigate the effect of PGE 2 as well as PGF 2 ex: on the dista] half of the non-pregnant human fallopian tube obtained at different phases of menstrual cycle. 'Present address: Department of Pnvstoloqv, Faculty of Medicine, University of Peradeniya, Srt Lanka
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FFECTSOF PROSTAGLANDINS AND El ON THE CONTRACTILlTV …

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Page 1: FFECTSOF PROSTAGLANDINS AND El ON THE CONTRACTILlTV …

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FFECTSOF PROSTAGLANDINS F2ex: AND El ON THE CONTRACTILlTV OFNON-PREGNANT HUMAN FALLOPIAN TUBE IN VITRO

M.T.M. JIFFRY* AND P. VIRUTAMASEN

Department of Obstetrics and Gvneecoloqv.Chulalongkorn Hospital,

Rama IV Road, Bangkok- Thailand(Received on March 28. 1980)

Summary: The effects of PGF2ex: and PGE2 on the distal part of the isolated non-pregnanthuman fallopian tubes obtained from known menstrual phases has been investigated. Both PGF2COand PGE2 produced an increased contractility of failopian tube. However. PGF2cx: was found tobe more potent than PGE2 and also the contractions produced by the former compound showedwave forms of relatively high amplitude and low in frequency than that produced by the latter com-pound. These two compounds did not show a priming effect on each other. There was no dis-cernible effect of phase of the menstrual cycle upon the contractile response to PG.

Key words: prostaglandin F2ex: and El contractility non-pregnant human tallopian tube

INTRODUCTION

The excitability produced by prostaglandin F2ex: (PGF2ex:) on the myometrial andfallopian tubal musculature was undisputed. in human and animal studies conducted in vivoand in vitro (4.5.11). However. there were contradictory findings on the effect of the PGEserieson the uterine and fallopian tube musculature. Early in vitro studies on non-pregnanthuman myometrium indicated that PGE series exerted an antagonistic effect to that producedby PGF2ex: (1 2). However. later in vitro studies on pregnant and non-pregnant humanmyometrium showed increased contractility on exposure to PGE series (3.7.9). A fewin vivo studies on both pregnant and non-pregnant human myometrium also showedspasmogenic effects produced by intravenous administration of PGE (6.8). Similarly.in vitro studies conducted on non-pregnant human fallopian tube showed excitatory effectsat the proximal region and relaxation at the distal part due to PGE (9). In a later study.the same group demonstrated an increase in motility due to PGE. on the distal part of thenon-pregnant human fallopian tube in vitro. However. there were no recent studies doneto re-examine the reported contradictory findings on the effect of PGE on the distal part ofthe non-pregnant human fallopian tube obtained at known phases of the menstrual cycle.Therefore. the present investigation was conducted in vitro, as part of a continuous series ofexperiments to investigate the effect of PGE2 as well as PGF2ex: on the dista] half of thenon-pregnant human fallopian tube obtained at different phases of menstrual cycle.

'Present address: Department of Pnvstoloqv, Faculty of Medicine, University of Peradeniya, Srt Lanka

Page 2: FFECTSOF PROSTAGLANDINS AND El ON THE CONTRACTILlTV …

166 J iffry and Virutamasen July-September 19Ind. J. Phvsiol, Pharmac.

MATERIALS AND METHODS

Distal portions of non-pregnant human fallopian tubes were obtained from patientswho had undergone surgery of the uterus due to varied reasons. Specimens from patientswith lesions in the fallopian tubes were rejected. The menstrual phase of the patientswere assessed by the history.

The specimens were immediately placed in Tyrode's solution (137 mM-NaCI. 2.7mM-KC!. 1 mM-MgCb 0.35 mM-NaH2PO •.2H20, 12 mM-NaHC03, 1.8 mM-CaClz,5-mM-glucose). Thereafter a 2 cm )( 5 mm piece of the intermediate and inner musculartissue from the most distal end of the specimen was carefully dissected out. This prepara-tion was mounted in a muscle chamber filled with 50 m/ of Tyrode's solution at 3TC andallowed to stabilise while it was being bubbled with 5% C02 in 0" so that pH was 7.3-7.4.Contractions of the strips were recorded isometrically with a 50 9 strain gauge via an amplifierand pen recorder. Various concentrations of PGE2 and PGF2<x were ad~ed separately andallowed to act only for a maximum period of 3 minutes. After each exposure, the musclechamber was washed off twice with Tyrode's solution and allowed to stabilise again infresh Tyrode's solution.

RESULTS

All the seven specimens in this series showed excitability due to PGF.a: as well asPGE2and 50 nalm! and 100 ng/m/ respectively were found to bethe lowest concentrationsrequired to initiate a change in the contractility (Table I).

TABLE I: Threshold concentrations of PGF2OC. and PGE2 t~ initiate a change in contractility inthe distal part of the human fallopian tube at different phases of menstruation.

Specimen Day of the Lowest Lowestmenstrual cycle concentration of concentration of

PGF20C ng/ml E2 naimt

5 50 100

14 100 100

26 75 200

7 100 300

7 75 200

20 75 200

22 100 200

2

3

4

5

6

7

Figure I shows the increase in rhythmic contraction of the fallopian tube whenPGE2 was added to the solution in different concentrations. The characteristics of excitationproduced by PGE2 is different from that produced by PGF2<x. PGE2 produced spasmogenic

me 24ber 3et with reduced amplitude w

higher amplitude (Fig. 1)

200

,00

2'!3 rill\'!

Fig. 1 : compariof the n

In four specimens

presence of PGF1CX,therproduced as a result of Pp~esence of PGh

159 L2 5 min

Fig. 2 :

Page 3: FFECTSOF PROSTAGLANDINS AND El ON THE CONTRACTILlTV …

·f

s Wereobtained from patienns. Specimens from patiennstrual phase of the patien

e 243

t with reduced amplitude whereas PGF.cx:gher amplitude (Fig. 1)

PGF2cx: and PGE2 on Fallopian Tube 167

produced wave forms of low frequency with

200 300 400 500

solution (137 mM-NaC/. 2.7-Na~C03. 1.8 mM-CaCI2.r~edlate and inner musculardissected out. This prepara-

yrode's solution at 3JCC and0" so that pH Was 7.3-7.4

9 straingauge via an amplifie;were added separately and

er each exposure, the muscleallowed to stabilise again in

100 700 300

lity due to PGF.cx: as well asbethe lowest concentrations

a change in contractility inphasesof menstruation.

of Lowestconcentration ofI E2 ng/ml

100

100

200

300

200

200

200

Fig. 1: Comparison of the effect of PGE2 and PGF2cx: on the rhythmic contractionof the non-pregnant human fa//opian tube (distal part).

In four specimens obtained from different subjects, when PGE2 was added in thepresenceof PGF2a, there was no resultant increase in the excitation other than what wasproduced as a result of PGF2'X (Fig. 2). It was the same when PGFzcx: was added in thepesence of PGE2.

f= li. a

the fal/opian tube Whenaracteristics of excitation

E2 produced spasmogenic

F(g. 2 : Rhvrhrmc contraction of the isolated fa//opian tube on exposure toPGF2cx: (300 ng/ml) and PGE2 (400 ng/ml) together.

Page 4: FFECTSOF PROSTAGLANDINS AND El ON THE CONTRACTILlTV …

168 J iffry and Virutamasen July-September 1Ind. J. Physiel. Pha

e 24r 3. M Prestaglandirs and R'

Kanm. S.M.· MTP Press. 1975.(d) Lancester.e . . K Hillier. K. Somers

Kanm. S.M.M .• t . on uterine actiVityby different rou es Brit commonow.J Obstet Gynaec.· .

• . action of prostaglandl.Midak -: E. The d modificatien of thl"wus m v/tro an

37-550. 1970. With_Brandel. U. Bygdman. N. M.fleet 190 : 1970.

• A Ingelman-sundbergndberg. F.. F' lIopian tubes in vttrus and the a b

A In elman-sunder$andeberg. F.. . gd the fallepian

e human uterus and P W Ramwell. Prost

peroff. l. an .'1970.

DISCUSSION

It is evident from our findings that while confirming the classical excitatorv eftproduced by PGF2CX.PGE2also produced a definite excitatory effect on the distal part ofhuman fallopian tube. This is in contradiction to the findings of some other war(1.2.9) where they showed that the excitatory effect produced by PGE2 was confinedthe proximal region of the non-pregnant human fallopian tube and that in the distal regioproduced relaxation. However. PGEa needed a relatively higher concentration than tof PGF2cx to produce the same effect. Since the contradictory findings were only relato the distal region. we confined our investigations only to the distal region.

PGF2cx produced characteristic wave forms with higher amplitude and low frequenwhereas the PGE2 produced wave forms of low amplitude and higher frequency. characrising a spasmogenic nature.

When one prostaglandin (either PGE2 or PGF20") was introduced in the presencethe excitation effect produced by the other. there were no increase in the contraction pattdue to the second prostaglandin (either PGE2 or PGF2cx) This shows that although PGand PGF2CXproduced excitation when introduced separately. there were no priming effect0one prostaglandin on another (between PGE2 and PGF2CX). Furthermore. it should IJ.l

noted that since there were consistency in the contractions exerted by anyone type of PGin all the seven subjects. different phases of the menstrual cycle apparently do not producean effect on the response elicited by PGE1 and PGF2cx.

ACKNOWLEDGEMENTS

This study was conducted during the tenure of a UNFPA Fellowship offered toMTMJ. The authors wish to thank Prof. V. Basnayake of the Department of Physiology.Faculty of Medicine. University of Peradeniya for his comments. The assistance given byMr. RAD. Nicholas and Miss S. Mathiaparanam is appreciated.

REFERENCES

1. Bygdman. M. and R. Eliasson. A comparative study on the effect of different prostaglandin compounds en themotility of the isolated human myometrium. Medna Exp.• 9 : 409-415. 1963.

2. Bygdman. M. The effect of prostaglandins on human myometrium in vitro. Acta Pbvstot. Scend., 23 : Suppl:242 : 1-78. 1964.

3. Embrey. M.P. and D.L. Morrison. The effect of prostaglandin on human pregnant myometrium.Gynae. Brit. Commonw .. 75 : 829-832. 1968.

4. Embrey. M.P. Prostaglandins. In. Scientific Foundations of Obstetrics and Gynaecology. Philipp. EE et. al. (ed.)London. William Heineman Medical Books Ltd .• 803-820. 1977.

Page 5: FFECTSOF PROSTAGLANDINS AND El ON THE CONTRACTILlTV …

/nd. me 24ber 3

PGFloc and PGEl on Fallopian Tube 169

nfirming the c/asSica .excitatory eft I exc/tatory effe

ecr on th d'the findin e Istal part ofgs of some h

produced by PGE or er Work. 2 Was c f'ien tube and that in . On tnedtlve/y higher the d,stal region

concentrat"ntradictory find in s Ion than thaIy to the distal r g. Were only relat

eglon.

~ higher amplitude andttudeand higher fre low frequency,

quency, characte_

Karim. S.M.M. Prostaglandins and Reproduction. In. advances in Prostaglandin Research. Karim, S.M.M.(ed). Lancester. MTP Press. 1975.Karim,S.M.M.. K. Hillier. K. Somers and R. Trussell. The effect of prostaglandins El and F2ex:: administeredby different routes on uterine activity and the cardiovascular system in pregnant and non-pregnant women.J. Obstet. Gynaec. Brit. Commonow .. 78 : 172-178. 1971.Midak. E. The action of prostaglandin El (PGE1) on human pregnant (at the time of labour) and non-pregnantuterusin vitro and modification of this action by adrenergic receptor blocking agents. Acta Physiol. Pot; 24 :537-550. 1970.Hoth-Brandel. U. Bygdman. N. M. Wiqvist and S. Bergstrom. Prostaglandin for induction of therapeutic abortion.Lancet 190 : 1970.

. Sandberg. F., A. Ingelman-Sundberg and G. Ryden. The effect of prostaglandins E2 and El on the humanuterusand the Fallopian tubes in vitro. Acta Obstet. Gynaec. Scand., 43 : 95-102, 1963.

C. Sandeberg. F.• A. Ingelman-Sunderberg and G. Ryden. The effect of prostaglandin Flex::' FI, Fz and Fl onthe human uterus and the fallopian tubes in vitro. Acta. Obstet. Gynaecol. Scand., 44 : 585-594, 1965.

1. Speroff, L. and P.W. Ramwell. Prostaglandins in Reproductive Physiology. Am. J. Obst. Gynae., 107: 1111-1130,1970.

) Was intrOduced .noincrease' h In the presence of

In t e cant .) This Shows th ractlon patterntely th at although PGE. ere Were no . . 2F2ex). FUlth pr,mtng effect of

ermore it hnsexerted by an '. s ould b~al cycle apparen;'y o~e type of PG

o not produce

a UNFPA Fellow h'f the 0 s Ip offered to

epartment of Ph .ments Th . YSlology. e assIst . .iated. ance gIVen by

different prost I .5. 1963 ag andln compOund. s on theo. Acta Physlol. Scand., 23

: SuPp/. :

an pregnant mYometrium.J. Obstet.

d GynaeCology. Ph.,.IIPP. EE et. a/. (ed.)