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J Senior

Publications and source records attributed to J Senior.

At least 19 recordsLinked to original sources
PubMed1992

In vitro characterization of prostanoid FP-, DP-, IP- and TP-receptors on the non-pregnant human myometrium.

1. Prostaglandin F (PGF), PGD, PGI and thromboxane A2 (TXA2) receptors have been pharmacologically characterized on the non-pregnant human myometrium in vitro in accordance with the receptor classification proposed by Coleman et al. (1984). The tools for the classification include both natural prostanoids, synthetic, selective analogues and antagonists where available. 2. The potent excitatory actions of the natural FP-receptor prostanoid, PGF2 alpha, and the synthetic analogue, fluprostenol, indicate the presence of FP-receptors mediating contraction on the human myometrium. 3. PGD2 produced a biphasic response consisting of excitation followed by relaxation of spontaneous activity of the myometrium. The selective DP-receptor agonists, BW245C, produced purely inhibitory responses illustrating the presence of inhibitory DP-receptors in this tissue. The inhibitory responses of both PGD2 and BW245C were antagonized by the competitive DP-receptor antagonist, BWA 868C, providing conclusive evidence for the existence of DP-receptors. 4. PGI2 produced a biphasic response similar to PGD2. Iloprost, the EP1/IP-receptor agonist also produced a biphasic response, whilst the IP-receptor selective agonist, cicaprost, caused inhibition only, suggesting that inhibitory IP-receptors exist in the non-pregnant human myometrium. 5. The TXA2-mimetic, U46619, produced marked stimulation of the non-pregnant human myometrium and was approximately equipotent to PGF2 alpha and fluprostenol in this effect. The actions of U46619 were competitively antagonized by the TP-receptor antagonist GR32191 showing that excitatory TP-receptors exist in this tissue.6. All prostanoids tested, both natural and synthetic, had activity on the non-pregnant human myometrium in vitro, supporting the existence of a heterogeneous population of prostanoid receptors in this tissue. If the results from the present study are combined with those previously reported for EP-receptor agonists (Senior et al., 1991), it may be concluded that excitation may occur through FP-, TP-, EP3- and few EP,-receptors, whereas inhibition may occur through DP-, IP- and EP2-receptors.

Female↗
PubMed1992

The role of thromboxane in the uterotrophic response in the gravid normotensive and spontaneously hypertensive rat.

The role of thromboxane in the gravid normotensive (CD) and hypertensive (SHR) rat was investigated (by utilizing two thromboxane receptor-blocking drugs, EP092 and AH23848) both at mid-gestation and at term. The parameters examined were uterine blood flow (blood flows were measured by the microsphere technique) and uterine weight and placental blood flow at term, fetal mass and number. At mid-gestation EP092 significantly (P < 0.005) increased uterine blood flow in both strains whilst the increases seen with AH23848 were not statistically significant. At term (day 22 in the CD and day 23 in the SHR rat) the antagonists increased uterine blood flow in the CD rats alone. However, at this time the antagonists caused an increase in placental blood flow in both strains. Thromboxane appears to be involved in the regulation of uteroplacental blood flow. The observation that the antagonists were able to potentiate blood flow by mid-gestation may provide a clinical indication with respect to potential prophylactic use of this class of compounds in cases of pregnancy-induced hypertension in women.

Animals↗
PubMed1992

A comparison of the uterotrophic response in cyclic and ovariectomized normotensive and spontaneously hypertensive rats.

The uterotrophic response in the normotensive (CD) and the hypertensive (SHR) rat was compared in intact cyclic rats and in ovariectomized rats given oestradiol. The parameters measured were blood flow, and uterine wet and dry weights. In the cyclic animals blood flow to the oestogen target tissue varied throughout the oestrous cycle, peak flows being achieved at pro-oestrus; in the SHR rat, however, the pro-oestrous maximum was significantly attenuated compared with the CD rat. Uterine wet and dry weights were similar. The temporal response to oestradiol in ovariectomized rats showed that in the CD rat the hyperaemic response peaked earlier than in the SHR rat, significant changes in terms of increased water imbibition also occurred more quickly in the CD strain. In both strains, uterine dry weight was the last parameter to be significantly increased, the maximum weight being attained more quickly in the SHR rat. The results of this study indicated that it is the blood flow to the oestrogen target tissues of the uterus and vagina that is most susceptible to change with strain of rat.

Animals↗
PubMed1991

Influence of surface hydrophilicity of liposomes on their interaction with plasma protein and clearance from the circulation: studies with poly(ethylene glycol)-coated vesicles.

Well-defined liposome systems have previously established the influence of size, surface charge lipid composition and surface ligands, on in vivo fate and behaviour of model compounds entrapped in liposomes. In the present study, preformed liposomes which quantitatively retain aqueous markers were covalenty coupled via dipalmitoylphosphatidyl-ethanolamine, to the hydrophilic polymer, monomethoxypoly(ethylene glycol) (MPEG 5000). Such liposomes retain the coating in the presence of plasma, and appear to adsorb plasma components more slowly than liposomes without the polymer, shown using an aqueous two-phase partitioning technique. MPEG-coupled liposomes were cleared from the blood circulation up to 30% more slowly than liposomes without MPEG after intravenous administration to mice, despite the unmodified liposomes being of a composition and size shown previously to favour achievement of maximum half-life. It is suggested that the polymer acts as a surface barrier to plasma factors which otherwise bind to liposomes in the blood and accelerate vesicle removal.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1991

The effects of thromboxane receptor antagonists on oestrogen-induced uterotrophic responses in the spontaneously hypertensive rat.

1. The possible role of thromboxane in the uterotrophic response to oestrogen, in the spontaneously hypertensive rat was investigated by use of the thromboxane receptor antagonists EP092, AH23848 and BM 13.505. 2. The parameters studied were uterine blood flow (measured by the microsphere technique), uterine wet and dry weights and the concentrations of cytosolic and nuclear oestrogen receptors. 3. The antagonists attenuated oestradiol-induced uterine blood flow and significantly reduced both wet and dry uterine weight. These changes were accompanied by decreases in nuclear oestrogen receptor levels. 4. The results suggest a supportive role for thromboxane in oestradiol-induced uterine growth.

Animals↗
PubMed1991

Modification of the rat uterine response to oestrogen and tamoxifen by thromboxane antagonists.

1. The thromboxane receptor antagonists EP092, AH23848 and BM 13.505 were used to investigate the role of thromboxane in the uterotrophic response to oestradiol and tamoxifen. 2. The parameters examined were uterine blood flow (measured by the microsphere technique), uterine wet and dry weights and the concentrations of cytosolic and nuclear oestrogen receptors. 3. Only EP092 potentiated the hyperaemic response to oestrogen but all three thromboxane antagonists inhibited oestradiol-stimulated uterine growth. This inhibition was accompanied by a decrease in nuclear oestrogen receptor concentration. 4. The uterotrophic response to tamoxifen was unaffected by the thromboxane antagonists. 5. The mechanism by which the thromboxane antagonists may be exerting their growth inhibitory effect is discussed, although, whether this effect can be attributed to blockade of thromboxane receptors or to some other mechanism is not clear from this study.

Animals↗
PubMed1991

In vitro characterization of prostanoid EP-receptors in the non-pregnant human myometrium.

1. Prostaglandin receptors of the PGE type have been characterized in the non-pregnant human myometrium in vitro according to the scheme of Coleman et al. (1984) by use of the agonists PGE2, sulprostone, rioprostil, AY23626, butaprost, misoprostol, 16,16-dimethylprostaglandin E2, enprostil and iloprost, and, the antagonist AH6809. 2. All prostanoids tested were active in non-pregnant human myometrium either as stimulators and/or inhibitors of spontaneous activity or both. Biphasic responses to PGE2 indicate that at least two receptor types of the EP-receptor exist, one mediating relaxation and the other mediating contraction. 3. Further evidence for the EP-receptor mediating excitation and relaxation was provided by the action of the EP2-/EP3-receptor selective prostanoids rioprostil, AY23626 and misoprostol, and the EP1-/EP2-receptor selective agonist 16,16-dimethylprostaglandin E2. 4. Butaprost, an EP2-receptor selective agonist, produced potent inhibition of spontaneous activity in the tissue which was generally longer-lasting than that evoked by the natural prostanoid PGE2. 5. The EP1-/EP3-receptor selective agonist sulprostone and the EP3-receptor agonist enprostil produced potent contractile responses supporting the presence of contractile EP3-receptors in the non-pregnant human myometrium in vitro. 6. The EP1-/IP-receptor selective agonist, iloprost, produced mixed responses in non-pregnant human myometrium. The contractile response was inhibited by the EP1-receptor antagonist AH6809. However, responses to the EP1-/EP3-receptor selective agonist sulprostone were unaffected by AH6809 which may indicate that only a small population of EP1-receptors is present. 7. Therefore it would seem that a heterogeneous population of EP-receptors is present in the non-pregnant human myometrium.

Dinoprostone↗
PubMed1978

Modification of oestrogen-induced uterine hyperaemia by drugs in the ovariectomized rat.

Uterine blood flow in ovariectomized rats was measured by means of radioactive microspheres. Blood flow was increased from 55 ml min-1 100 g-1 by treatment (i.v.) with 0.5 microgram oestradiol kg-1 and reached 680 ml min-1 100 g-1 within 60 min. This oestrogen-induced increase of blood flow was reduced significantly by pretreatment with mepyramine (a histamine H1-receptor antagonist), cellulose sulphate (a kininogen-depleting agent) and aprotinin (a kininogenase inhibitor). Cimetidine (a histamine H2-receptor antagonist), kallikrein (kininogenase enzyme) and atropine (an anticholinergic drug) had no effect on the increased uterine blood flow. Indomethacin and AH 7170, which inhibit the formation of prostaglandins, also caused a lower increase in uterine blood flow. None of the pretreatments fully inhibited the oestrogen-induced increase in blood flow, suggesting that more than one mediator may be involved.

Animals↗
PubMed1976

Plasma kininogen during the oestrous cycle, early pregnancy and pseudopregnancy in the rat.

1. Changes in the plasma kinin precursor, kininogen, occur following treatment with oestrogens and progestogens. This work was undertaken to attempt to relate plasma kininogen values to hormonal changes in various reproductive states. 2. During the oestrous cycle kininogen concentrations follow a nychthemeral rhythm, kininogen depletion occurring during the increase in general activity of the rat. 3. Superimposed on the nychthemeral changes in kininogen concentration are changes which may be related to the hormonal events of the oestrous cycle. 4. During early pregnancy and pseudopregnancy the kininogen level rises; this increase may be due to changes in the circulating levels of oestrogens and progestogens. 5. It is suggested that the changes in kininogen concentration may result from utilization of kinin which could be of functional significance.

Animals↗
PubMed1976

The influence of drugs on the kinin-forming system in relation to pregnancy and parturition in the rat.

The duration of normal gestation and parturition in the rat can be changed by treatment with drugs which alter the equilibrium of the kallikrein-kinin system. The kallikrein inhibitor, aprotinin, when given from Days 19-22 of pregnancy prolongs gestation. Treatment with aprotinin from Days 20-22 of pregnancy prolongs the parturient process, as does a single dose given on the morning of Day 22. Kallikrein, when administered from Days 19-22 of pregnancy, results in a prolongation of gestation and abolishes the pre-parturient behaviour ('labour'). Parturition is prolonged and many fetuses are stillborn. Soya bean trypsin inhibitor when given from Days 19-22 of pregnancy delays and prolongs parturition; maternal haemorrhage occurs during birth and many fetuses are born dead or are abandoned at birth. It is suggested that the kallikrein-kinin system plays a functional role in the normal process of parturition in the rat.

Animals↗