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1.
《Prostaglandins》1981
Possible mechanisms accounting for the inhibition of acid secretion by prostaglandins were studied using cells dispersed from canine fundic mucosa by enzymes and enriched in the content of parietal cells by elutriation. The accumulation of 14C-aminopyrine (AP) was used as an index of parietal cell response to stimulation. PGE2 inhibited histamine-stimulated AP uptake, with 50% inhibition (ID50) found at 10 nM, but did not block the response to carbachol, gastrin, or dibuturyl cyclic AMP. PGE2 did, however, inhibit aminopyrine uptake stimulated by carbachol and gastrin when the response to these agents was potentiated by histamine. PGE2, at namomolar concentrations, also inhibited histamine-stimulated cyclic AMP production. When mucosal cells were treated with only PGE2 at concentrations above 1 μM, stimulation of cyclic AMP production was found. In cell separation studies with the elutriator rotor, PGE2 appeared to stimulate cyclic AMP production primarily in nonparietal cells.Prostacyclin (PGI2) and two stable analogues, 6β-PGI1 and the 16-phenoxy analogue (5α)5,9-epoxy-16-phenoxy-PGF1, also specifically inhibited histamine-stimulated AP accumulation. PGI2 required relatively high concentrations for this effect (ID50 = 1 μM), whereas the 16 phenoxy derivative was much more potent in its inhibition of histamine-stimualted AP accumulation (ID50 = 10 nM), with this difference probably accounted for by the rapid degradation of PGI2 compared to the stable 16-phenoxy analogue. All three of these prostanoids also inhibited histamine-stimulated cyclic AMP production. As was found with PGE2, at high concentrations and in the absence of histamine PGI2 and PGI1 also stimulated cyclic AMP production. However, the 16-phenoxy analogue failed to stimulate cyclic AMP production either in the parietal cell enriched fractions or in the nonparietal cell fractions.These data indicate that PGE2 and prostacyclin analogues are potent, direct and specific inhibitors of histamine-stimulated parietal cell function and that it is the inhibition, rather than the stimulation, of cyclic AMP formation that is linked to the antisecretory actions of the prostanoid compounds. 相似文献
2.
Paul Mangeat Jacques Marvaldi Ounissa Ait Ahmed Guy Marchis-Mouren 《Regulatory peptides》1981,1(6):397-414
Vasoactive intestinal peptide (VIP), secretin, catecholamines and prostaglandin E1 (PGE1) in the presence of a cyclic nucleotide phosphodiesterase inhibitor stimulate the accumulation of cyclic AMP in two colorectal carcinoma cell lines (HT 29 and HRT 18) with subsequent activation of the cyclic AMP-dependent protein kinases. In HT 29 cells incubated without phosphodiesterase inhibitor, 10?9 M VIP promotes a rapid and specific activation of the low cyclic AMP phosphodiesterase (1.7-fold); at 25°C the effect is maintained for more than 15 min, while at 37°C the activity returns to basal value within 15 min. As shown by dose-response studies, VIP is by far the most effective inducer () of the cyclic AMP phosphodiesterase activity; partial activation of the enzyme is obtained by 3 · 10?7 M secretin, 10?5 M isoproterenol and 10?5 M PGE1; PGE2 and epinephrine are without effect. In HRT 18 cells VIP is less active () whereas 10?6 M PGE1, 10?6 M PGE2 and 10?5 M epinephrine are potent inducers of the phosphodiesterase activity. The positive cell response to dibutyryl-cyclic AMP further indicates that cyclic AMP is a mediator in the phosphodiesterase activation process. The incubation kinetics and dose response effects of the various agonists on the cyclic AMP-dependent protein kinase activity determined for both cell types in the same conditions show a striking similarity to those of phosphodiesterase. Thus coordinate regulation of both enzymes by cyclic AMP was observed in all incubation conditions. 相似文献
3.
A.K. Goff J. Zamecnik M. Ali D.T. Armstrong 《Prostaglandins & other lipid mediators》1978,15(5):875-879
The ability of prostaglandin I2 (PGI2) to stimulate cyclic AMP production by granulosa cells, isolated from intact immature rats, has been demonstrated in vitro. The minimal effective dose was 15 ng/ml, which was comparable to the minimal effective dose for PGE2. However, a concentration of 15 μg/ml PGI2 was required to stimulate cyclic AMP production maximally, compared to a concentration of 1 μg/ml PGE2, which produced the maximum response. It therefore appears that PGI2 is not more effective than PGE2 in stimulating cyclic AMP production in granulosa cells, and is possibly less effective. Submaximal concentrations of PGI2 appeared to be able to modify the stimulation of cyclic AMP production by follicle- stimulating hormone (FSH), but whether or not PGI2 plays any role in follicular function remains to be established. 相似文献
4.
Rat anterior pituitary explants were incubated with PGI2, PGH2 and PGE2 in the presence of theophylline (1mM) and the production of cyclic AMP was measured. PGE2 was found to be about 20 times more potent than PGI2 while PGH2 was slightly more effective than PGI2. The results suggest that PGI2 does not play a physiological role in cyclic AMP mediated events in the rat anterior pituitary. 相似文献
5.
Rat anterior pituitary explants were incubated with PGI2, PGH2 and PGE2 in the presence of theophylline (1mM) and the production of cyclic AMP was measured. PGE2 was found to be about 20 times more potent than PGI2 while PGH2 was slightly more effective than PGI2. The results suggest that PGI2 does not play a physiological role in cyclic AMP mediated events in the rat anterior pituitary. 相似文献
6.
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
7.
Marc E. Goldyne Jan ke Lindgren Hans-Erik Claesson Sven Hammarstrm 《Prostaglandins & other lipid mediators》1980,19(1):155-163
Prostaglandins (PG)E1, E2 and I2 were produced by polyoma virus transformed (py) 3T3 fibroblasts. The levels of PGE1, PGE2 and 6-keto-PGF1α (degradation product of PGI2) were 22.7, 225 and 33.2 ng/ml medium, respectively, 72 h after medium change. The stimulatory potencies of exogenous PGE1, PGE2 and PGI2 on adenosine 3′:5′-monophosphate (cyclic AMP) formation were similar. Therefore, the prostaglandin mediated increase in cyclic AMP levels observed during growth of these cells (Claesson, H.-E., Lindgren, J.Å. and Hammarström, S. (1977) Eur. J. Biochem.
, 13) is largely (>80%) mediated by PGE2 and to lesser extents by PGE1 and PGI2. 相似文献
8.
O.V. Miller J.W. Aiken D.P. Hemker R.J. Shebuski R.R. Gorman 《Prostaglandins & other lipid mediators》1979,18(6)
Prostacyclin (PGI2) dose-dependently increases the adenosine 3′,5′-cyclic monophosphate (cyclic AMP) levels in canine femoral, carotid, and canine and bovine coronary arteries. The prostacyclin-stimulation is enhanced by phosphodiesterase inhibitors, and is readily measurable after 60 sec incubation. The prostaglandin endoperoxide PGH2, but not PGH1, also elevates cAMP levels in femoral arteries. Inhibition of arterial prostacyclin synthetase with 28 μM 9,11-azoprosta-5,13-dienoic acid (azo analog I) blocks the PGH2-stimulation of cAMP accumulation. Azo analog I does not attenuate a direct PGI2 stimulation, indicating that the PGH2 dependent elevation of cAMP is due to conversion of PGH2 to PGI2 by the artery. PGI2 and PGE1 increase cyclic AMP levels and relax dog femoral and bovine coronary arteries, while PGE2, which actually contracts bovine coronary arteries, has no effect on arterial cyclic AMP levels. The significance of the PGI2-stimulation of arterial cyclic AMP is not known, but it is probably related to relaxation of arterial strips. 相似文献
9.
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
10.
Effects of prostaglandin E1(PGE1) and prostaglandin I2(PGI2) on the mechanical activity and tissue cyclic AMP content of the longitudinal muscle of rabbit intestine were examined, comparing that of isoproterenol. PGE1 or PGI2 caused a contraction and did not affect the tissue cyclic AMP content. Isoproterenol caused a relaxation and increasedtissue cyclic AMP content. 相似文献
11.
Albert Ratner Melba C. Wilson Glenn T. Peake 《Prostaglandins & other lipid mediators》1973,3(4):413-419
The studies reported here confirm the previously observed potent stimulus to growth hormone (GH) secretion by prostaglandin E1 (PGE1). Proportional increments in GH secretion were observed following addition of PGE1 over a concentration range of 10?7 to 10?5 M. Growth hormone secretion could not be further stimulated by higher concentrations of prostaglandin. Prostaglandin E1 also increased cyclic AMP concentration in the pituitary explants in a proportional fashion, which correlated closely with its potency as a growth hormone secretogogue. In order to define more precisely the mechanism by which prostaglandin acts, the effects of prostaglandin antagonist, 7-oxa-13-prostynoic acid, on GH secretion and cyclic AMP accumulation were investigated. Addition of the antagonist alone had no consistent effects on GH secretion or cyclic AMP levels in the pituitary. However, the antagonist significantly reduced the stimulation of hormone release and cyclic AMP accumulation found following addition of PGE1. Increasing the concentration of antagonist further diminished prostaglandin stimulated hormone release and nucleotide accumulation. The antagonist failed to block the stimulatory effects of theophylline and dibutyryl cyclic AMP on GH release, indicating that the inhibition observed occurred prior to intracellular accumulation of the cyclic nucleotide. These results are consistent with the hypothesis that a prostaglandin receptor on the pituitary somatotrope is linked to the adenyl cyclase-cyclic AMP system. 相似文献
12.
Steven M. Taffet Thomas E. Eurell Stephen W. Russell 《Prostaglandins & other lipid mediators》1982,24(6):763-774
Mouse resident peritoneal macrophages stimulated
by purified bacterial lipopolysaccharide (LPS) produced both prostaglandin E2 (PGE2) and prostaglandin I2 (PGI2), the latter detected as its stable metabolite, 6-keto PGF1α. Maximum production, induced in each case by 1 ng/ml purified LPS, was in the range of 10−7M for PGI2 and 3 × 10−8M for PGE2. A quantitatively similar increase in intracellular levels of macrophage cyclic AMP (measured on a whole cell basis), with a similar duration of effect, was stimulated by PGE2 and PGI2; however, only PGE2 had a negative regulatory effect on macrophage activation for tumor cell killing. These data confirm that more than a whole cell increase in the concentration of cyclic AMP is needed to shut off nonspecific tumor cell killing mediated by LPS-activated resident peritoneal macrophages. 相似文献
13.
The effects of prostaglandins on human monocyte chemotaxis were studied . None of the prostaglandins tested, including members of the A, B, E or F series, were chemotactic for monocytes. Prostaglandin E2 however, enhanced the chemotactic responsiveness of monocytes to complement - activated human serum by almost 200%. The enhancement of chemotaxis was not directly related to the ability of PGE2 to raise intracellular cyclic AMP levels. These studies support a role for prostaglandins as modulators of the inflammatory response. 相似文献
14.
Aviv Hassid 《Prostaglandins & other lipid mediators》1981,21(6):985-1001
Renal tubular epithelial cells isolated from dog and pig kidney (MDCK and LLC-PK1, respectively) transport water and electrolytes in culture. MDCK cells resemble collecting tubule cells by additional, but not all, morphologic and biochemical criteria. It has previously been reported that PGE2 appears to regulate transport activity by MDCK cells as well as their proliferation. We investigated prostaglandin biosynthesis by MDCK and LLC-PK1 cells and assessed the effects of peptide hormones, bradykinin and vasopressin, on the cells' prostaglandin biosynthesis. Thin-layer chromatography of radioactive products released by MDCK cells labelled with octatritiated of [14C] arachidonic acid indicated the presence of materials comigrating with PGE2, PGI2 (detected as 60oxo0PGF1α) and PGF2α, in decreasing order of abundance. Maclofenamate inhibited the biosynthesis of all radioactive peaks comigrating with PGs, thus confirming their identities as product of fatty acid cyclo-oxygenase activity. The chemical identities of [3H] PGE2 and [3H] 6-oxo-PGF1α made by the cells were further confirmed by treatment with KOH. Radioimmunoassay of culture fluids incubated with MDCK cells verified that PGE2 was the most abundant prostaglandin. Tranylcypromine, thought to be a specific inhibitor of prostacyclic synthetase, inhibited PGE2 as well as PGI2 biosynthesis indicating a lack of specificity of the inhibitor. The observation of PGE2 and PGF2α as respectively the most and least abundant prostaglandinds made by MDCK was in disagreement with results from another laboratory in which the reverse order of abundance was found. This suggests the presence of more than one cell line identified as MDCK but having different biochemical properties.Bradykinin stimulated acylhydrolase activity as well as PGE2 and PGI2 biosynthesis in MDCK cells while vasopressin had little or no effect. These results support the hypothesis that bradykinin's natriuretic effects may be mediated by prostaglandinds and that vasopressin is unlikely to acutely stimulate prostaglandin biosynthesis in collecting tubule cells . Endogenous PGE2 may also regulate the proliferation of MDCK cells in culture.In contrast to MDCK cells, LLC-PK1 cells lacked significant prostaglandin biosynthetic capability as documented by radiometric thin-layer chromatography and radioimmunoassay. This suggests that prostaglandins may have a modulatory rather than an obligatory role in regulating transport activity by tubular epithelial cells. 相似文献
15.
Both intact cortical tissue and isolated cortical cells from the adrenal gland of the rat were analyzed for 6-keto-PGF1α, the hydrolysis metabolite of PGI2, using high-performance liquid chromatography and gas chromatography-mass spectrometry. 6-Keto-PGF1α was present in both incubations of intact tissue and isolated cells of the adrenal cortex, at higher concentrations than either PGF2α or PGE2. Thus, the cortex does not depend upon vascular components for the synthesis of the PGI2 metabolite. Studies , using isolated cortical cells exposed to 6-keto-PGF1α (10?6-10?4M), show that this PG does not alter cAMP levels or steroidogenesis. Cells exposed to PGI2 (10?6-10?4M), however, show a concentration-dependent increase of up to 4-fold in the levels of cAMP without altering corticosterone production. ACTH (5–200 μU/ml) increased cAMP levels up to 14-fold, and corticosterone levels up to 6-fold, in isolated cells. ACTH plus PGI2 produced an additive increase in levels of cAMP, however, the steroidogenic response was equal to that elicited by ACTH alone. Adrenal glands of the rat perfused with PGI2 showed a small decrease in corticosterone production, whereas ACTH greatly stimulated steroid release. Thus, while 6-keto-PGF1α is present in the rat adrenal cortex, its precursor, PGI2, is not a steroidogenic agent in this tissue although it does stimulate the accumulation of cAMP. 相似文献
16.
Preparations of small and large steroidogenic cells from enzymatically dispersed ovine corpora lutea were utilized to study the effects of luteinizing hormone (LH) and prostaglandins (PG) E1, E2 and I2. Cells were allowed to attach to culture dishes overnight and were incubated with either LH (100 ng/ml), PGE2, PGE2, or PGI2 (250 ng/ml each). The secretion of progesterone by large cells was stimulated by all prostaglandins tested (P < 0.05) while the moderate stimulation observed after LH treatment was attributable to contamination of the large cell population with small cells. Prostaglandins E1 and E2 had no effect on progesterone secretion by small cells, while LH was stimulatory at all times (0.5 to 4 hr) and PGI2 was stimulatory by 4 hr. Additional studies were conducted to determine if the effects of PGE2 upon steroidogenesis in large cells were correlated with stimulated activity of adenylate cyclase. In both plated and suspended cells PGE2 caused an increase (P < 0.05) in the rate of progesterone secretion but had no effect upon the activity of adenylate cyclase or cAMP concentrations within cells or in the incubation media. Exposure of luteal cells to forskolin, a nonhormonal stimulator of adenylate cyclase, resulted in marked increases in all parameters of cyclase activity but had no effect on progesterone secretion. These data suggest that the actions of prostaglandins E1, E2 and I2 are directed primarily toward the large cells of the ovine corpus luteum and cast doubt upon the role of adenylate cyclase as the sole intermediary in regulation of progesterone secretion in this cell type. 相似文献
17.
18.
Jia-Huey Yu Herbert Wells William J. Ryan Jr. Weldon S. Lloyd 《Prostaglandins & other lipid mediators》1976,12(4):501-513
Prostaglandins of the E-series (PGE1 and PGE2) may be involved in disease-related, localized loss of bone. E-prostaglandins increase the cyclic AMP content of many cells; and, to determine if their effects on bone are mediated by cyclic AMP, we examined the effects of E-prostaglandins and of other agents on the cyclic AMP content of cultured bone cells. PGE2 produced a rapid, marked and dose-related increase in the cyclic AMP content of confluent monolayers of bone cells isolated from newborn rat calvaria. At 2.8 × 10−6 M, PGE1 and PGE2 had approximately the same effect, while the effect of PGF2α was much less pronounced. In the presence of theophylline, PGE2 had a more marked effect than parathyroid hormone (PTH) and the combination of PGE2 and PTH had a synergistic effect. The divalent, cationic, ionophore, A23187, produced an increase in cellular cyclic AMP and had an additive effect in combination with PGE2. Synthetic salmon calcitonin (CT), which inhibits the bone resorptive effect of PGE2, increased cellular cyclic AMP and had an additive effect in combination with PGE2. A prostaglandin antagonist, SC-19220, partially inhibited the resorptive effect of PGE2 and reduced its effect on cellular cyclic AMP. The calcium antagonist, D600, inhibited the bone resorptive effects of PGE2 but had no effect on increased cellular cyclic AMP produced by PGE2.The marked effect of PGE2 on bone cell cyclic AMP suggests that this action is involved in the mechanism of PGE2-related bone loss. The fact that agents with different effects on PGE2-induced increases in cellular cyclic AMP can inhibit its resorptive actions, suggests that PGE2-induced changes in cyclic AMP may be related less to its resorptive actions than to its inhibitory effect on bone formation. 相似文献
19.
Sara S. Tynan Niels H. Andersen Max T. Wills Laurence A. Harker Stephen R. Hanson 《Prostaglandins & other lipid mediators》1984,27(5):683-696
The ω-chain variant analogs of prostacyclin (PGI2) and PGD2 in which the n-amyl side-chain has been replaced by a cyclohexyl group have been prepared and their cardiovascular activities have been compared to those of BW-245C(Fig. 1)(1) a potent anti-aggregatory vasodilator bearing a cyclohexyl-terminated side-chain on a hydantoin skeleton. The cyclohexyl group has little effect on PGI2, but converts PGD2 to a long lasting hypotensive agent and increases the platelet anti-aggregatory potency of PGD2 by a factor of 8. The prostaglandin antagonist N-0164 selectively blocks the anti-aggregatory actions of PGD2, cyclohexyl-PGD2, and BW-245C; with essentially no effect on PGI2, cyclohexyl-PGI2 and PGE2 at comparably effective doses. The latter observation is contrary to an earlier report by MacIntyre (2,3), but supports the view that the anti-aggregatory effect of high doses of PGE2 () is mediated by the PGI2 receptor (4). The hydantoin acts at the platelet PGD2 receptor. 相似文献
20.
Effects of parathyroid hormone (PTH) and several prostaglandins (PGs) on cyclic AMP (cAMP) metabolism were studied and compared in isolated renal cortical tubules from male hamsters. Both production and intracellular degradation of cAMP were increased by PTH and each of the PGs tested (PGE2, PGE1, PGI2). Production of cAMP was increased to similar levels by maximal concentrations of PTH and each PG, however, degradation of cAMP was significantly higher in response to PTH than with any of the PGs. This difference in intracellular degradation of cAMP was responsible for the much higher concentrations of cAMP in renal cortical tubules exposed to PGs (PGE1, PGE2, PGI2) than to PTH. Submaximal amounts of each PG produced additive increases in cAMP concentrations in the presence of maximal amounts of PTH. Additivity of the combined responses was lost, however, as the PGs concentrations reached their maximas. The results suggest that renal PGs (PGE2 and PGI2) may modulate the effects of PTH on cAMP concentrations in renal cortical tubules. 相似文献