ProstaglandinsPub Date : 1997-03-01DOI: 10.1016/S0090-6980(97)00012-9
Wolf-Juergen Buhl, Liisa M. Eisenlohr , Ulrich Gehring
{"title":"Phospholipase A2 in human placental serum","authors":"Wolf-Juergen Buhl, Liisa M. Eisenlohr , Ulrich Gehring","doi":"10.1016/S0090-6980(97)00012-9","DOIUrl":"10.1016/S0090-6980(97)00012-9","url":null,"abstract":"<div><p>Intervillous blood was collected from term placentae at delivery, and sera were tested for phospholipase A<sub>2</sub> under various experimental conditions. Enzyme activity was found to develop upon extended storage in the cold or at 37°C. The enzyme is reversibly inhibited by dithiothreitol, requires Ca<sup>++</sup> ions for activity, and tolerates various detergents. The apparent molecular weight is 42 kDa. In all these parameters the serum enzyme behaves similar to the 42 kDa phospholipase A<sub>2</sub> which we recently purified to homogeneity from thoroughly washed placental tissue. Serum phospholipase A<sub>2</sub> appears to be generated by proteolytic processing from a slightly larger inactive precursor which was detected immunochemically. Most likely this protein originates from fetal cells and may be released by membrane damage. We conclude that both placental serum and tissue harbour a novel type of phospholipase A<sub>2</sub> which is distinct from cytosolic and secretory phospholipases A<sub>2</sub>. Preference for arachidonate containing substrate suggests a role in eicosanoid production within gestational tissues.</p></div>","PeriodicalId":20653,"journal":{"name":"Prostaglandins","volume":"53 3","pages":"Pages 139-152"},"PeriodicalIF":0.0,"publicationDate":"1997-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0090-6980(97)00012-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20080394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ProstaglandinsPub Date : 1997-03-01DOI: 10.1016/S0090-6980(97)00014-2
Xue-Jun Li , He-ming Yu , Samuel S. Koide
{"title":"Effect of mifepristone and antiestrogens on uterine PGF2α and PGE2 concentrations in ovariectomized and pregnant rats","authors":"Xue-Jun Li , He-ming Yu , Samuel S. Koide","doi":"10.1016/S0090-6980(97)00014-2","DOIUrl":"10.1016/S0090-6980(97)00014-2","url":null,"abstract":"<div><p>Four antiestrogens (anordiol, tamoxifen, RU 39411, ICI 182780) and the antiprogestin, mifepristone (RU 486), were administered to the following three animal models: (1) ovariectomized rats, (2) mated rats treated post-coitally; and (3) pregnant rats treated post-implantation. The antiestrogens were administered alone or in combination with mifepristone at doses effective in preventing and/or terminating pregnancy in rats. The objective of the study was to determine whether these drugs influenced uterine concentrations of prostaglandins (PGF<sub>2α</sub> and PGE<sub>2</sub>).</p><p>Antiestrogens administered alone to ovariectomized rats did not effect uterine PGE<sub>2</sub> or PGF<sub>2α</sub> concentrations; whereas the combination of anordiol/mifepristone increased uterine PGF<sub>2α</sub> concentration, resulting in an increase in the PGF<sub>2α</sub>/PGE<sub>2</sub> ratio.</p><p>Mated rats were treated post-coitally for three consecutive days with anordiol, tamoxifen, estradiol and mifepristone alone and with the combination of anordiol/mifepristone and tamoxifen/mifepristone. An increase in uterine PGF<sub>2α</sub> concentrations and in the PGF<sub>2α</sub>/PGE<sub>2</sub> ratio occurred only in anordiol/mifepristone treated group. A decrease in uterine PGE<sub>2</sub> concentrations occurred in animals treated with anordiol, tamoxifen and estradiol, resulting in an increase in the PGF<sub>2α</sub>/PGE<sub>2</sub> ratio.</p><p>Anordiol (5.0 mg/kg/day) and mifepristone (4.0 mg/kg/day) alone and the combination of anordiol/mifepristone (2.5/1.0 mg/kg/day) administered to pregnant rats on days 7, 8 and 9 of pregnancy induced an increase in PGF<sub>2α</sub> levels without affecting uterine PGE<sub>2</sub> concentration. The changes in uterine PGF<sub>2α</sub> concentrations induced by anordiol and the combination of anordiol/mifepristone resulted in an increase in the PGF<sub>2α</sub>/PGE<sub>2</sub> ratio.</p><p>The antiestrogens tested except for ICI 182780 possessed agonist activity when assayed by measuring their capacity to increase the uterine weights in ovariectomized rats. Also, ICI 182789 was the only antiestrogen that did not influence uterine PG concentrations. It can be concluded that ICI 182780 is the only “pure” antiestrogen among those tested.</p><p>The present results show that antiestrogens and the combination of mifepristone plus anordiol at doses preventing implantation and terminating pregnancy increase uterine PGF<sub>2α</sub> and/or decrease PGE<sub>2</sub> concentrations, resulting in an alteration of PGF<sub>2α</sub>/PGE<sub>2</sub> ratio. These findings suggest that there exists a critical balance of PGF<sub>2α</sub> to PGE<sub>2</sub> concentrations in the uterus required for the normal passage of fertilized ova through the oviduct, initiating implantation of the blastocysts, development of embryos, and maintenance of pregnancy.</p></div>","PeriodicalId":20653,"journal":{"name":"Prostaglandins","volume":"53 3","pages":"Pages 187-197"},"PeriodicalIF":0.0,"publicationDate":"1997-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0090-6980(97)00014-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20152048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ProstaglandinsPub Date : 1997-03-01DOI: 10.1016/S0090-6980(97)00011-7
Bruce E. Rapuano, Richard S. Bockman
{"title":"Protein kinase C-independent activation of a novel nonspecific phospholipase C pathway by phorbol myristate acetate releases arachidonic acid for prostaglandin synthesis in MC3T3-E1 osteoblasts","authors":"Bruce E. Rapuano, Richard S. Bockman","doi":"10.1016/S0090-6980(97)00011-7","DOIUrl":"10.1016/S0090-6980(97)00011-7","url":null,"abstract":"<div><p>The effects of phorbol myristate acetate, an activator of protein kinase C, on the release of [<sup>3</sup>H]arachidonic acid and prostaglandin synthesis were studied in an osteoblast cell line (MC3T3-E1). Phorbol myristate acetate (20 uM) liberated 16 and 55% of the [<sup>3</sup>H]arachidonate in prelabeled phosphatidylinositol and phosphatidylethanolamine, respectively, and evoked a 19-fold stimulation in the synthesis of prostaglandin E<sub>2</sub>. Phorbol myristate acetate doubled the cellular mass of 1,2-diacylglycerol and stimulated the liberation of [<sup>3</sup>H]arachidonate from the diacylglycerol pool in prelabeled cells. The diacylglycerol lipase inhibitor RHC 80267 blocked 75–80% of the phorbol ester-promoted (total) cellular liberation of [<sup>3</sup>H]arachidonic acid and production of prostaglandin E<sub>2</sub>. In comparison, the release of [<sup>3</sup>H]arachidonate from phosphatidylethanolamine (but not phosphatidylinositol) was only partially antagonized (to the same degree) by the PLA<sub>2</sub> inhibitor p-bromophenacylbromide and the protein kinase C inhibitor Et-18-OMe. PMA-induced formation of diacylglycerol or synthesis of PGE<sub>2</sub> was not affected by the prior inhibition of protein kinase C. Therefore, we have shown a novel pathway for the liberation of arachidonic acid in osteoblasts involving the nonspecific hydrolysis of phosphatidylinositol and phosphatidylethanolamine by phospholipase C followed by the deesterification of diacylgycerol. This pathway can be activated by a phorbol ester through a protein kinase C-independent mechanism.</p></div>","PeriodicalId":20653,"journal":{"name":"Prostaglandins","volume":"53 3","pages":"Pages 163-186"},"PeriodicalIF":0.0,"publicationDate":"1997-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0090-6980(97)00011-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20080396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Distribution of prostaglandin E receptors in the rat gastrointestinal tract","authors":"Min Ding , Yoshikazu Kinoshita , Kiyohiko Kishi , Hirohisa Nakata , Sazzad Hassan , Chiharu Kawanami , Yukihiko Sugimoto , Masato Katsuyama , Manabu Negishi , Shuh Narumiya , Atsushi Ichikawa , Tsutomu Chiba","doi":"10.1016/S0090-6980(97)00015-4","DOIUrl":"10.1016/S0090-6980(97)00015-4","url":null,"abstract":"<div><p><span><math><mtext>Aims</mtext></math></span>: In order to study the role of prostaglandin in the regulation of the gastrointestinal functions, gene expression of prostaglandin receptors along the rat gastrointestinal tracts were investigated.</p><p><span><math><mtext>Methods</mtext></math></span>: Rats were used for the study. The combination of counterflow elutriation separation of mucosal cells and Northern blot analysis was used to detect the gene expression of prostaglandin receptors in gastrointestinal tracts.</p><p><span><math><mtext>Results</mtext></math></span>: In small intestine and colon, prostaglandin E2 EP1 and EP3 receptor mRNAs were mainly localized in the deeper intestinal wall containing muscle layers. EP4 receptor gene expression, on the other hand, was detected in the intestinal mucosal layer.</p><p>In the stomach, EP1 mRNA was detected in gastric muscle layers, whereas EP3 and EN receptor gene expression was mainly present in the gastric mucosal layer containing epithelial cells. In gastric epithelial cells, parietal cells were found to have both EP3 and EP4 receptors. At lower concentrations, prostaglandin E2 inhibited gastric acid secretion by parietal cells probably through EP4 receptors. At higher concentrations, however, it stimulated it. On the other hand, mucous cells possessed only EP4 receptor mRNA.</p><p><span><math><mtext>Conclusions</mtext></math></span>: Thus, it is suggested that prostaglandin E2 modulates gastrointestinal functions through at least three different prostaglandin receptors (EP1, EP3, and EP4), each of which has a distinct distribution in the gastrointestinal tract.</p></div>","PeriodicalId":20653,"journal":{"name":"Prostaglandins","volume":"53 3","pages":"Pages 199-216"},"PeriodicalIF":0.0,"publicationDate":"1997-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0090-6980(97)00015-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20152049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nitric oxide stimulates prostaglandin synthesis in cultured rabbit gastric cells","authors":"Hironori Uno, Tetsuo Arakawa, Takashi Fukuda, Hidenori Yu, Yasuhiro Fujiwara, Kazuhide Higuchi, Masayasu Inoue , Kenzo Kobayashi","doi":"10.1016/S0090-6980(97)00013-0","DOIUrl":"10.1016/S0090-6980(97)00013-0","url":null,"abstract":"<div><p>Both prostaglandins (PGs) and nitric oxide (NO) have cytoprotective and hyperemic effects in the stomach. However, the effect of NO on PG synthesis in gastric mucosal cells is unclear. We examined whether sodium nitroprusside (SNP), a releaser of NO, stimulates PG synthesis in cultured rabbit gastric mucus-producing cells. These cells did not release NO themselves. Co-incubation with SNP (2 × 10<sup>−4</sup>, 5 × 10<sup>−4</sup>, 10<sup>−3</sup> M) increased PGE<sub>2</sub> synthesis, and SNP (10<sup>−3</sup> M) increased PGI<sub>2</sub> synthesis in these cells. Hemoglobin, a scavenger of NO, (10<sup>−5</sup> M) eliminated the increase in PGE<sub>2</sub> synthesis by SNP, but methylene blue, an inhibitor of soluble guanylate cyclase, (5 × 10<sup>−5</sup> M) did not affect the increase in PGE<sub>2</sub> synthesis by SNP. 8-bromo guanosine 3′ : 5′-cyclic monophosphate (8-bromo cGMP), a cGMP analogue, (10<sup>−6</sup>, 10<sup>−5</sup>, 10<sup>−4</sup>, 10<sup>−3</sup> M) did not affect PGE<sub>2</sub> synthesis. These findings suggest that NO increased PGE<sub>2</sub> and PGI<sub>2</sub> synthesis via a cGMP-independent pathway in cultured rabbit gastric cells.</p></div>","PeriodicalId":20653,"journal":{"name":"Prostaglandins","volume":"53 3","pages":"Pages 153-162"},"PeriodicalIF":0.0,"publicationDate":"1997-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0090-6980(97)00013-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20080395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"7,7-Difluoroprostacyclin derivative, AFP-07, a highly selective and potent agonist for the prostacyclin receptor","authors":"Chang-Sheng Chang , Manabu Negishi , Takashi Nakano , Yoshitomi Morizawa , Yasushi Matsumura§ , Atsushi Ichikawa","doi":"10.1016/S0090-6980(97)00003-8","DOIUrl":"10.1016/S0090-6980(97)00003-8","url":null,"abstract":"<div><p>Recently, we cloned cDNAs for the prostacyclin receptor (IP) and the four mouse PGE receptor subtypes, EPI, EP2, EP3 and EN, and established Chinese hamster ovary cells that stably express each receptor. We examined the agonist potency and selectivity of AFP-07, a 7,7-difluoroprostacyclin derivative, compared with widely used stable prostacyclin analogue, iloprost, using the cells expressing each cloned receptor. AFP-07 strongly displaced the [<sup>3</sup>H] iloprost binding to the IP receptor-expressing cell membranes, the half maximal concentration for the displacement being 3 nM, which was one order lower than that of iloprost. AFP-07 concentration-dependently stimulated CAMP formation in the IP-expressing cells, the half-maximal concentration for the stimulation being 10 pM which was one order lower than that of iloprost. On the other hand, AFP-07 showed lower affinity for EP1, EP2, EP3 and EN than PGE2, but iloprost had the same affinity as PGE<sub>2</sub> for the EPl. These results demonstrate that AFP-07 is a potent and highly selective agonist for the IP receptor.</p></div>","PeriodicalId":20653,"journal":{"name":"Prostaglandins","volume":"53 2","pages":"Pages 83-90"},"PeriodicalIF":0.0,"publicationDate":"1997-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0090-6980(97)00003-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20061296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}