PRODUCTION OF THROMBOXANE B2 BY INTRA-UTERINE TISSUES FROM PREGNANT GOATS IN VITRO

1978 ◽  
Vol 78 (1) ◽  
pp. 159-160 ◽  
Author(s):  
M. D. MITCHELL ◽  
A. P. F. FLINT ◽  
E. J. KINGSTON ◽  
G. D. THORBURN ◽  
J. S. ROBINSON

Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU (Received 9 February 1978) It has been shown that prostaglandins play an important role in the mechanism of parturition in many species, including the goat (Currie & Thorburn, 1977; Thorburn, Challis & Robinson, 1977). Recently we have demonstrated that intra-uterine tissues from pregnant goats, when superfused in vitro, produce prostaglandins E and F (PGE, PGF) and 13,14-dihydro-15-oxo-prostaglandin F at various rates (Mitchell, Flint, Robinson & Thorburn, 1978). The exciting discoveries of two potent prostaglandin-like compounds, thromboxane A2 (TXA2; Hamberg, Svensson & Samuelsson, 1975) and prostacyclin (PGI2; Moncada, Gryglewski, Bunting & Vane, 1976), have radically altered our thinking on prostaglandins and basic data are urgently required concerning these compounds. Since prostaglandin endoperoxides are the immediate precursors of both prostaglandins and TXA2 (and PGI2) and since TXA2 has been shown to cause contraction of a number

1978 ◽  
Vol 79 (3) ◽  
pp. 403-404
Author(s):  
M. D. MITCHELL ◽  
J. S. ROBINSON

Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU (Received 21 July 1978) Prostaglandins of the E and F series have been shown to relax or contract respectively guinea-pig trachea and recently it has been demonstrated that the prostaglandin endoperoxides PGG2 and PGH2 (immediate precursors of prostaglandins E and F) have far greater potency in contracting tracheal smooth muscle than prostaglandin F (Hamberg, Svensson, Hedqvist, Strandberg & Samuelsson, 1976). Furthermore, both thromboxane A2 and prostacyclin can also elicit contraction of the trachea with thromboxane A2 being considerably more active (Omini, Moncada & Vane, 1977; Svensson, Strandberg, Tuvemo & Hamberg, 1977). Administration of thromboxane A2 has been shown to raise the tracheal insufflation pressure in guinea-pigs (Svensson et al. 1977) and indeed its stable metabolite thromboxane B2 is released in relatively large amounts from sensitized guinea-pig lungs when challenged with antigen (Dawson, Boot, Cockerill,


1978 ◽  
Vol 79 (3) ◽  
pp. 401-402 ◽  
Author(s):  
M. D. MITCHELL ◽  
A. P. F. FLINT ◽  
B. R. HICKS ◽  
E. J. KINGSTON ◽  
G. D. THORBURN ◽  
...  

Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Headington, Oxford, 0X3 9DU (Received 21 July 1978) It now seems likely that prostaglandins play an important role in the mechanisms of parturition in many species (Flint & Hillier, 1976; Thorburn, Challis & Robinson, 1977), including the goat (Thorburn, Nicol, Bassett, Shutt & Cox, 1972; Currie & Thorburn, 1977). This evidence has been further strengthened by the demonstration of the production of prostaglandins in vitro by uterine tissues from goats during late pregnancy (Mitchell, Flint, Robinson & Thorburn, 1978b). The recent discovery of prostacyclin (Moncada, Gryglewski, Bunting & Vane, 1976) has added a new dimension to prostaglandin research since in some biological systems it has a greater potency than other prostaglandins (Moncada et al. 1976; Omini, Moncada & Vane, 1977). Prostacyclin is highly unstable in aqueous media and degrades spontaneously to 6-oxo-prostaglandin F1α (6-oxo-PGF1α; Johnson, Morton, Kinner, Gorman,


1978 ◽  
Vol 78 (3) ◽  
pp. 453-454 ◽  
Author(s):  
I. C. McMILLEN ◽  
G. JENKIN ◽  
G. D. THORBURN ◽  
J. S. ROBINSON

Nuffield Institute for Medical Research and Nuffield Department of Obstetrics and Gynaecology, John Radcliffe Hospital, Headington, Oxford, 0X3 9DU (Received 6 April 1978) Growth hormone (GH) has been located in the ovine foetal pituitary gland by day 50 of gestation (Stokes & Boda, 1968). The concentration of GH in the plasma of foetal sheep is ten times higher than the postnatal value, increasing from 40 ng/ml on day 100 of gestation to 100–120 ng/ml on day 140 (Bassett, Thorburn & Wallace, 1970). After foetal hypophysectomy, the concentration of GH falls to < 2 ng/ml, indicating that it originates in the foetal pituitary gland (Wallace, Stacey & Thorburn, 1973). Labelled GH does not cross the ovine placenta (Wallace et al. 1973). After sectioning the foetal pituitary stalk, the concentration of GH in the foetal plasma drops to approximately 5 ng/ml (Wallace et al. 1973), which implies that the secretion of GH


1981 ◽  
Vol 59 (9) ◽  
pp. 915-920 ◽  
Author(s):  
Kenneth Wong ◽  
Karen Freund

Exogenous prostaglandins E1 and E2 and L-isoproterenol potently inhibited the production of superoxide anions by human neutrophils activated in vitro by n-formylmethionyl-leucyl-phenylalanine (FMLP). An estimated ID50 of 50 nM was found for all three agents while L-epinephrine and prostaglandin F2α were 10 and 100 fold, respectively, less active. Inhibition occurred whether these agents were added before, together with, or after the addition of the tripeptide to cell suspensions. Cells treated with dibutyryl adenosine 3′,5′-monophosphate also expressed reduced rates of superoxide synthesis thus suggesting that the hormonal inhibitors acted indirectly by stimulating membrane bound adenylate cyclase.


1980 ◽  
Vol 43 (01) ◽  
pp. 038-040 ◽  
Author(s):  
L C Best ◽  
T K Holland ◽  
P B B Jones ◽  
R G G Russell

SummaryPlatelet aggregation, secretion of 5-hydroxy tryptamine and production of thromboxane B2 were monitored simultaneously in human platelet suspensions in the absence and presence of cyclooxygenase or thromboxane synthetase inhibitors. Aggregation, secretion and thromboxane B2 formation in response to either sodium arachidonate or epinephrine were blocked by aspirin or by 1-N-butyl imidazole suggesting that thromboxane biosynthesis was an essential requirement for platelet activation by these agents. In contrast, thrombin and collagen could apparently induce aggregation and secretion via two pathways: at low doses involving thromboxane production, but at higher doses by a direct mechanism independent of thromboxane biosynthesis. In the case of ADP, inhibition of thromboxane production blocked secretion but had little effect on aggregation, indicating that secretion was probably dependent on thromboxane biosynthesis which probably occurred as a result of aggregation. Thus it appears that although the processes of thromboxane production, release of dense granule constituents and aggregation may often be intimately linked, each process can occur independently of the other, depending upon the stimulus used.


1978 ◽  
Vol 79 (3) ◽  
pp. 393-394 ◽  
Author(s):  
R. GUNASEGARAM ◽  
K. L. PEH ◽  
P. C. T. CHEW ◽  
S. M. M. KARIM ◽  
S. S. RATNAM

Department of Obstetrics and Gynaecology, University of Singapore, Kandang Kerbau Hospitalfor Women, Singapore 8, Republic of Singapore (Received 3 May 1978) From the previous studies of Bloch & Benirschke (1959, 1962) and Plotz, Kabara, Davis, LeRoy & Gould (1968) it appears that at mid-term, human foetal adrenal glands are capable of synthesizing C21- and C19-steroids de novo from acetate and cholesterol. Villee, Engel, Loring & Villee (1961), however, incubated slices and homogenates of foetal adrenal gland with [2-14C]acetate or [4-14C]cholesterol and could not demonstrate the incorporation of radioactivity into these steroids. Moreover, perfusion studies by three groups of investigators indicated only minute conversions of the same radioactive substrates into neutral steroids in the foetal adrenal glands (Solomon, Bird, Ling, Iwamiya & Young, 1967; Telegdy, Weeks, Archer, Wiqvist & Diczfalusy, 1970a; Telegdy, Weeks, Lerner, Stakemann & Diczfalusy, 1970b). It is widely believed that steroid hormones are normally synthesized from acetate via


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