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1.
The effects of 19-hydroxy-prostaglandins (19-OH-PGs) were tested on the rabbit oviduct and uterus and on the rhesus monkey () uterus. The 19-OH-PGEs suppressed spontaneous oviductal and uterine activity in the rabbit. The qualitative effect on the rabbit oviduct of 19-OH-PGEs was similar to that of PGE2. However, the typical response of the rabbit uterus to PGE2 was an increase in muscle activity. With regard to the rabbit oviduct, 19(R)-OH-PGE2 was as potent as PGE2, but 19(S)-OH-PGE2 was approximately as potent as PGE2. Based on the dose of 19-OH-PGEs usually required to cause a minimal suppression and the dose of PGE2 required to cause a minimal stimulation of rabbit uterine activity, 19(R)-OH-PGE2 was twice as potent as PGE2 while 19(S)-OH-PGE2 was as potent as PGE2. Stimulatory effects on the rabbit oviduct and uterus were observed following administration of 19-OH-PGEs and PGF2α. The potency on the rabbit oviduct of 19(S)-OH-PGF2α was about to that of PGF2α; the potency of 19(R)-OH-PGF2α was about to that of PGF2α. Both 19-OH-PGFs were approximately to as potent as PGF2α on the rabbit uterus. At the doses tested 19-OH-PGFs were inactive on the monkey uterus. Thus, these compounds are at least as active as PGF2α. In contrast, 19(R)-OH-PGE2 had approximately the same potency as PGE2 in stimulating monkey uterine activity; but 19(S)-OH-PGE2 was approximately as potent as PGE2. 相似文献
2.
Niels H. Andersen Shoji Imamoto Donald H. Picker 《Prostaglandins & other lipid mediators》1977,14(1):61-101
With the report given herein all diastereomers of PGF2, PGE2, and PGD2 which bear the naturally recognized 15-S hydroxylated center, whether in the natural or -prostanoic acid skeleton, have been prepared by a route involving initial introduction of the carboxyl (α) chain (1). A major advantage of the initial α-ylation+ route is the facile reduction of the 13,14-en-15-one system with methanolic NaBH4 which proceeds without competing 1,4-reduction. The products are thus free of 13,14-dihydro-PG2 contaminants (2). The initial pharmaco logical evaluation of these diastereomers will be submitted for publication in this journal (3). 相似文献
3.
The activity of prostaglandins (PG) in producing vascular permeability was quantitated by dye extraction method in skin of anaesthetized rabbits. PGE1 and PGE2 (0.01–10 μg) produced increase in vascular permeability. Activity was approximately equal to that of histamine (Hist) and of that of bradykinin (BK) on a weight basis. The activity of PGF1α and PGF2α was only of that of PGE1 or PGE2.In spite of the relatively low potency of PGE1 and PGE2 in the rabbit, near threshold doses (0.1 or 1 μg) of PGE2 could potentiate permeability responses to bradykinin (0.1 μg) by 10 or 100-fold, respectively. Equivalent doses (0.1 or 1 μg) of histamine could not potentiate the bradykinin responses. Arachidonic acid (AA) at 1 μg, produced a 10-fold potentiation in the permeability response to bradykinin (0.1 μg). Pretreatment of the rabbits with indomethacin (20 mg/kg, i.p.) reduced the responses of BK (0.1 μg) + AA (1 μg) down to a similar magnitude of those seen with bradykinin alone. However, indomethacin did not block responses to either, BK alone, BK + PGE2, or BK + Hist. Various doses (1, 10, 100 and 300 μg) of arachidonic acid alone also produced increase in cutaneous vascular permeability, although its potency was only – of that of PGE2. This activity of arachidonic acid was attributed in part to its bioconversion to PGE2, since its activity was significantly reduced by the prostaglandin antagonist, diphloretin phosphate (DPP) (60 mg/kg, i.v.) and by indomethacin (20 mg/kg, i.p.), which blocks conversion of arachidonic acid to prostaglandins. Arachidonic acid may owe some of its permeability increaseing effects to histamine release, since its effects were also reduced by the antihistamine, pyrilamine (2.5 mg/kg, i.v.). 相似文献
4.
Mats Hamberg Per Hedqvist Kjell Strandberg Jan Svensson Bengt Samuelsson 《Life sciences》1975,16(3):451-461
The effect on smooth muscle of the endoperoxides PGG2 and PGH2, which are intermediates in prostaglandin biosynthesis, was studied in different systems and . On gastrointestinal smooth muscle (gerbil colon, rat stomach) PGG2 and PGH2 produced contractions comparable to those of PGE2 and PGF2a whereas contractions elicited on vascular (rabbit aorta) and airway (guinea-pig trachea) smooth muscle were considerably greater than those of PGE2 and PGF2a respectively. On intravenous injection into guinea-pigs PGG2 and PGH2 caused a triphasic change in blood pressure and were 8–10 times more effective than PGF2a in producing an increase in tracheal insufflation pressure. When given as aerosols the unstable endoperoxides were less effective than PGF2a. It is concluded that the endoperoxides are potent smooth muscle stimulants and that they are more effective than their degradation products (PGD2, PGE2, PGF2a) in some systems. 相似文献
5.
M.J. Peek I.S. Fraser C.A. Phillips T.M. Resta P.M. Blackwell R. Markham 《Prostaglandins & other lipid mediators》1985,29(1):3-18
Two methods for measuring human endometrial prostaglandin production were compared. Endometrial samples from eight patients were incubated over eight hours by a perifusion and a superfusion technique. The collected fractions were assayed by radioimmunoassay for PGE2 and PGF2α.There was no significant difference between the perifusion and superfusion methods for the pattern and amount of PGE2 and PGF2 production with time. Significantly higher production levels of PGE2 and PGF2α were found in secretory phase endometria than in proliferative phase endometria. Histological examination of the tissue specimens by light and electron microscopy showed that both methods caused gross tissue damage after eight hours experimentation. The superfusion method produced more morphological damage than the perifusion method. However, no tissue damage could be detected after one hour of incubation with either method.Over an eight hour period neither the perifusion nor the superfusion technique appears to be a good indicator of endometrial prostaglandin production. Either reflect the situation. 相似文献
6.
The modulating effects of the E and F series prostaglandins upon the cAMP and cortisol output of normal human adrenal dice were evaluated with time and compared to the effects of ACTH. PGE1 and PGE2 significantly increased human adrenal cAMP levels; cortisol output increased in a dose related manner. Although the cortisol levels produced by E prostaglandins and ACTH were quantitatively similar, on a molar basis ACTH was greater than 106 fold more effective. PGE1α, PGF2α, PGF1β and PGF2β depressed adrenal cAMP, except PGF2α and PGF2β at 100 μg/ml. PGF1α and PGF2α depressed cortisol levels at all doses. Similarly, PGF1β and PGF2β also depressed cortisol output, except PGF2β at 100 μg/ml which was stimulatory. In both series of prostaglandins the temporal responses were dose related in regard to the cyclic nucleotide and steroid alterations. The findings demonstrate the E and F series prostaglandins act antagonistically in respect to cAMP and cortisol output. In addition, as the cAMP level and cortisol output are not always correlated, it appears that these prostaglandin mediated events are separable. The relationship between adrenal prostaglandins and cyclic nucleotides, therefore, invites a more sophisticated second messenger concept in terms of adrenocortical function, than currently proposed. 相似文献
7.
PGE1 and PGE2 significantly increased human adrenal cAMP levels ; cortisol output was also increased in a dose related fashion. In contrast, PGF1a and PGF2a depressed adrenal cAMP (except PGF2a at 100 μg/ml). PGF1a and PGF2a depressed cortisol levels at all doses. Indomethacin or 7-oxa-13-prostynoic acid did not affect these parameters. However, when applied in conjunction with ACTH they inhibited or enhanced hormonal action depending upon the temporal sequence of application. The findings indicate that prostaglandins modulate ACTH-adrenocortical cell interaction bidirectionally, initially potentiating and subsequently depressing ACTH stimulated events. 相似文献
8.
The ability of various prostaglandins (PGs) to affect the anamnestic immune response of keyhole limpet hemocyanin (KLH)-primed rabbit popliteal lymph node cells was investigated. Of the four PGs studied (PGA1, PGE2 and PGF2α), PGE1 was found to have a stimulatory effect, whereas PGA1, PGE2 and PGF2α were ineffective in stimulating or inhibiting the anamnestic response. Under the conditions studied, a 3.5-fold increase in antibody production was obtained in PGE1-treated, KLH-stimulated cultures. Maximum enhancement was obtained when 0.2 μg of PGE1 were added at the time of culture initiation and were allowed to remain in contact with the lymph node cells for 24 hours. 相似文献
9.
L. Hamberger L. Nilsson B. Dennefors I. Khan A. Sjögren 《Prostaglandins & other lipid mediators》1979,17(4):615-621
Human corpora lutea of defined ages were excise at operation cut into pieces and incubated in the presence of HCG, PGF2α and PGE2 alone or in combination. Following incubation cAMP formation in tissue and medium was determined. HCG-stimulated tissue cAMP content was most pronounced at a corpus luteum age of 7–10 days after ovulation. This stimulation was antagonized by PGF2α in corpora lutea older than 6 days. PGE2 stimulated cAMP formation and this effect was more pronounced when HCG and PGE2 were combined. A possible role for PGF2α as a luteolytic substance in the human is suggested. 相似文献
10.
Alam Farzad Neal S. Penneys Abdul Ghaffar Vincent A. Ziboh Jean Schlossberg 《Prostaglandins & other lipid mediators》1977,14(5):829-837
The biosynthesis of PGE2 and PGF2α was measured in intact peritoneal exudate preparations obtained fom -treated and control C3H mice. Although both the control and stimulated preparations biosynthesized PGF2α and PGE2 from [1–14C] arachidonic acid, the stimulated preparations generated more of both prostaglandins than did nonstimulated preparations, probably as a result of increased synthesis within macrophages. Increased transformation of PGE2 into PGF2α 9-ketoreductase was noted in stimulated preparations when compared to that in control cells. The data suggest that stimulated macrophages are capable of generating increased quantities of PGF2α and therefore might function as one source of this substance in resolving inflammatory reactions. 相似文献
11.
M.F. Gimeno A.M. Franchi M. Chaud E.T. Gonzalez M. Viggiano A.L. Gimeno 《Prostaglandins & other lipid mediators》1984,27(5):737-752
The output prostaglandins (PHs) E1, E2 and F2 α, from ampullary and isthmic portions of sow oviducts isolated during proestrus, estrus and metestrus, was explored. Moreover, cumulative dose-response curves for the contractile effect of these three PGs, on identical oviductal segments, were constructed. Isthmic preparations form proestrous and metestrous animals released more PGE1 and PGF2 α than PGE2 “like material”. During estrus, the outputs of PGE1, PGE2 and PGF2 α were similar, whereas, oviducts from proestrous and metestrous sows released less PGE1 and PGF2 α than during estrus. Although the output of PGE2 “like material” from isthmic and ampullary segments did not differ significantly during the three stages of the sex cycle, ampullary metestrous preparations released more PGE1 and PGF2 α, than estrous or proestrous ones. The addition of PGE1, PGE2 α, consistently stimulatedthe amplitude of contractions of isthmic oviductal segments isolated from proestrous and metestrous sows. Within the concentration-range explored, dose-response curves for PGE2 and PGE1 were to the left of those for PGF2 α in the isthmus obtained before ovulation (proestrus) but not in segments isolated at later times (2–3 days) of the cycle (metestrus). The stimulatory dose-response curves for PGE1, or PGE2, in isthmic segments of metestrous preparations incubated with phentolamine (10?6M) were shifted to the right of controls not exposed to the adrenoreceptor blocker, whereas, the curve for PGF2 α without phentolamine, was identical to that obtained in its presence. PGE1 and PGE2 did not evoke significant contractile effects on oviductal ampullary protions from proestrous sows, wherea, PGF2 α was clearly stimulatory at concentrations of 10?9M and higher. In ampullary segments isolated after ovulation (metestrus) the threshold for contractile enhancement following PGF2 α was greater than during proestrus, whereas, PGE1 elicited a significant inhibition of contractions. The spontaneous contractile pattern exhibited by isthmic and ampullary oviductal regions, prior to and after ovulation, is discussed in terms of tissue PG generation and output and is compared with results regarding tubal motility following the exposure to exogenous PGs. 相似文献
12.
W.A. Hallett A. Wissner C.V. Grudzinskas R. Partridge J.E. Birnbaum M.J. Weiss F. Dessy 《Prostaglandins & other lipid mediators》1977,13(3):409-415
-16-methoxy-PGE2, PGA2, PGF2α, 11-deoxy PGE1, and 11-deoxy PGF1α have been prepared via the cuprate conjugate addition procedure. These congeners are less potent than the parent prostaglandins as stimulators of isolated gerbil colon contractions and as bronchodilators in the guinea pig Konzett assay. 相似文献
13.
John W. Wilks Kristi K. Forbes Jerome F. Norland 《Prostaglandins & other lipid mediators》1973,3(4):427-437
Prostaglandin F2α (PGF2α) did not alter the biosynthesis of progesterone by slices of luteinized rat ovaries when used in concentrations from 1 to 10,000 ng/ml of incubation medium; likewise, PGF2α did not affect the incorporation of acetate-1-14C into progestins. PGF1α, 15-keto PGF2α, and PGE1 did not alter the biosynthesis of progesterone by luteinized rat ovaries; PGE2 inhibited the production of progesterone when used at a concentration of 10 μg/ml, but not at lower doses. PGF2α in combination with luteinizing hormone (LH) enhanced the metabolism of progesterone to 20α-hydroxypregn-4-en-3-one in luteinized rat ovaries. Interestingly, PGF2α, at a high concentration of 10 μg/ml, did stimulate progesterone biosynthesis by slices of ovarian tissue from immature rats hormonally primed to simulate “pseudopregnancy,” suggesting a steroidogenic action of prostaglandins on the ovarian follicular or interstitial cell. PGF2α (10 μg/ml) did not stimulate the biosynthesis of progesterone or 20α-hydroxypregn-4-en-3-one by slices of rabbit corpora lutea or rabbit ovarian interstitial tissue. It is concluded that prostaglandins do not stimulate progestin biosynthesis in rat luteal tissue. 相似文献
14.
Cheryl M. Heesch Guillermo Valenzuela Barrie J. Hodgson 《Prostaglandins & other lipid mediators》1977,14(2):279-282
The effects of PGD2, PGF2α and PGE1 were studied on the circular muscle of post-ovulatory rabbit oviducts . PGE1 inhibited spontaneous contractile activity. Lower concentrations of PGD2 and PGF2α were stimulatory and higher concentrations were inhibitory. Since PGD2 may be produced in the oviduct, any hypothesis concerning the role of prostaglandins in the control of oviductal motility and ovum transport should include PGD2 as well as PGFs and PGEs. 相似文献
15.
Endometrial concentrations of prostaglandins F2α (PGF2α) and E2 (PGE2) were measured by specific radioimmunoassay in sheep, on day 14 of estrous cycle or pregnancy, during luteolysis (Day 16 of the cycle), and after implantation (Day 23 of pregnancy) : concentrations observed on day 14 of cycle and pregnancy were similar. During luteolysis, on day 16 of cycle, a consistent drop was noticed. If luteal regression did not occur, as a consequence of the presence of an embryo, endometrial concentrations of PGF2α on day 23, were twice those of day 14, and PGE2 remained unchanged. 2 hour incubations of endometrial caruncular tissue from 14 days cyclic or pregnant ewes resulted in de novo synthesis of PG which could be increased by Arachidonic Acid and inhibited by Indomethacin; during the first 30 min of incubation, the PGF2α synthesis was comparable for both endometrial tissues, whereas PGE2 synthesis was twice as great in pregnant endometrium. Fourteen and 23 day conceptuses had high PGF2α and PGE2 concentrations which were not due to maternal PG sequestration : PG synthesis which could be inhibited by Indomethacin was observed in incubated 14 day old embryos. Treatment of pregnant ewes from day 7 to day 22 after mating, either with Indomethacin (300 mg s.c. daily) or with Acetylsalicylic Acid (1 g I.V. daily) resulted in a sharp diminution of endometrial PG concentration and release, with no apparent effect on the establishment of pregnancy. These results tend to ascribe a less important role to PG during early pregnancy in sheep as compared with rodents, in terms of embryonic growth and implantation. 相似文献
16.
The following experiments were designed in order to examine the inter-relationships of various prostaglandins (PG's) and the adrenergic nervous system, in conjunction with blood pressure and heart rate responses, . Stimulation of the entire spinal cord (50v, 0.3–3 Hz, 1.0 msec) of the pithed rat increased blood pressure, heart rate and plasma epinephrine (EPI) and norepinephrine (NE) concentration (radioenzymatic-thin layer chromatographic assay). Infusion of PGE2(10–30 μg/kg. min, i.v.) suppressed blood pressure and heart rate responses to spinal cord stimulation while plasma EPI (but not NE) was augmented over levels found in control animals. PGI2 (0.03–3.0 μg/kg. min, i.v.) suppressed the blood pressure response to spinal cord stimulation without any effect on heart rate or the plasma catecholamine levels. PGE2 and PGF2α(10–30 μg/kg. min, i.v.) did not change the blood pressure, heart rate or plasma EPI and NE responses to the spinal cord stimulation although PGF2α disclosed an overall vasopressor effect during the pre-stimulation period. At the pre-stimulation period it was also observed that PGE2, PGF2α and PGI2, had a positive chronotropic effect on the heart rate, the cardiac accelerating effect of PGE2 was not abolished by propanolol. These studies suggest that in the rat, PGE2 and PGI2 modulate sympathetic responses, primarily by interaction with the post-synaptic elements — PGE2 on both blood vessels and the heart and PGI2 by acting principally on blood vessels. 相似文献
17.
Philippe Leroux Marie-Christine Tonon Sylvie Jégou Catherine Delarue François Leboulenger Pierre Netchitaílo Hubert Vaudry 《Prostaglandins & other lipid mediators》1981,21(4):599-608
A possible direct effect of prostaglandins on α-melanotropin (α-MSH) release at the level of the intermediate lobe of the frog pituitary was investigated using a perifusion system technique. The effect of prostaglandins was studied on both spontaneous and TRH-stimulated α-MSH secretion. No significant effect of PGE1, PGE2, PGF1α or PGF2α on basal release of α-MSH could be detected. Indomethacin did not alter the α-MSH release induced by TRH. Conversely a significant increase in TRH-induced α-MSH secretion was observed in the presence of 1 x 10?6M PGE1. This magnifying effect was directly related to the concentration of TRH for doses ranging from 1 x 10?8M to 1 x 10?6M. 相似文献
18.
At low concentrations (i.e., 10?12–10?9 mol/l), PGF1α and PGF2α very intensely stimulated both the DNA-synthetic and mitotic activities of hepatocytes in 4-day-old primary cultures of neonatral rat liver. DNA replication was more intensely enhanced by PGF2α than by PGF1α, whereas mitotic activity was nearly equally affected by the two prostaglandins. On the whole, the growth-promoting activity of PGF1α used by itself or in equimolar mixtures with other prostaglandins (. ., A1, E1, .) mimicked that of arachidonic acid we previously reported (1). On a molar basis, PGF2α by itself stimulated hepatocytes′ DNA synthesis is more powerfully than arachidonate did, and when used in equimolar mixtures with other prostaglandins was at least as potent as arachidonic acid. These observations establish prostaglandins of the F series as quite powerful commitment factors and, though by a lesser degree, also intracycle regulators for neonatal rat hepatocytes in primary culture. However, the understanding of the role(s) of prostaglandins of F and other series in the physiological control of hepatocytes′ proliferative activation must wait the clarification of their interaction(s) with other arachidonate derivative(s) and polypeptide growth factor(s) which also may be involved in the process. 相似文献
19.
We have compared the production of prostaglandins in fibroblast-like cells and endothelial cells in culture. Of the fibroblasts studied , SHE, BP6T and KD produce significant amounts of PGI2, PGE2 and PGF2F2 under optimal culture conditions, but only 3T3 and BHK produce TxA2 in addition to PGI2. The adult bovine aortic endothelial cells (ABAE) and fetal bovine heart endothelium (FBHE) synthesise PGI2 but not TxA2, either from endogenous or exogenous substrates. Both cultured endothelial cells and fibroblasts apparently lack 15-hydroxyprostaglandin dehydrogenase pathway and the ability to convert 6-Keto PGF1α into 6-Keto PGE1. PGI2 production by ABAE was 3–5 times that of FBHE, about twice that of SHE cells and 6–8 times that of or BP6T cells. Supernatants or media obtained from these cells inhibited aggregation of human platelet-rich plasma, a known biological effect of PGI2. This effect was abolished when cell monolayers were preincubated with indomethacin or tranylcypromine. RIA and chromatographic data of 6-Keto PGF1α from these experiments confirmed that the inhibition of platelet aggregation was due to the formation of PGI2. The production of all prostanoids by endothelial cells or fibroflasts was significantly higher during the exponential phase of growth as compared to confluent monolayers. We propose that fibroblasts or SHE can serve as useful experimental models for the study of metabolism and transport of PGI2 and/or TxA2 in cells of nonendothelial nature. 相似文献
20.
H. Thaler-Dao M. Ramonatxo M. Saintot J. Chaintreuil A.Crastes de Paulet 《Prostaglandins & other lipid mediators》1982,24(2):149-163
prostaglandin biosynthesis by uteri of ovariectomized rats and guinea pigs treated or untreated with oestradiol 17 β, administered subsutaneously, was measured by R.I.A. of PGF2α and PGE2. Incubations with [1-14C] arachidonic acid were also performed and labelled metabolites were analyzed by TLC. The main metabolite in rats was 6 keto PGF1α and in decreasing order of magniture, PGF2α and PGE2. In guinea pig PGF2ga was the main product. Ovariectomy in rats completely changed the pattern of synthesized prostanoids: PGI2 production was doubled when compared to cycling rats and PGE2 increased 10 fold. PGF2α walues were similar to the mean value measured during the cycle. OE2 treatment almost completely inhibited PGI2 synthesis and reduced PGE2 by half. Total PG synthesis in OE2 treated animals was decreased by 5 fold when compared to spayed rats. Endogenous PGFsα synthesis was slightly stimulated. In the guinea pig OE2 treatment of ovariectomized animals increased the total synthesis from 50 per cent. PGF2α was always the main metabolite. In conclusion OE2 regulation of uterine PG synthesis is depending on the animal species and cannot be explained by a unique effect on the cyclooxyhenase, but rather by an interplay on the various enzymes of the arachidonic acid cascade. 相似文献