Disease relevance of alprostadil

• Hypotension occurred in the clinic in 3.3 percent of men receiving alprostadil [1].
• The efficacy of alprostadil was similar regardless of age or the cause of erectile dysfunction, including vascular disease, diabetes, surgery, and trauma (P<0.001 for all comparisons with placebo) [1].
• Mice receiving PGE1 treatment do not develop interstitial nephritis, nor do they display delayed-type hypersensitivity (DTH) to the immunizing renal tubular antigen preparation [2].
• Platelets of a patient with type I Glanzmann's thrombasthenia bound [3H]2-methylthio-ADP and responded normally to ADP in the presence of PGE1 [3].
• The case reports of 492 infants with critical congenital cardiac disease treated with prostaglandin E1 (PGE1) were reviewed to determine the nature and incidence of intercurrent medical events [4].

Psychiatry related information on alprostadil

• CONCLUSIONS: In men with erectile dysfunction, transurethral alprostadil therapy resulted in erections in the clinic and in intercourse at home [1].
• The PGE1/DGLA ratio was low in intermittent explosive disorder [5].
• In patients with bulimia or anorexia nervosa, both initially and after weight gain, the maximal effect of prostaglandin E1 (PGE1) on platelet cAMP production was greatly increased, while the half-maximally effective dose was unchanged [6].
• CONCLUSIONS: Clinical improvements in erectile function due to alprostadil therapy were associated with improvements in sexual activity, sexual satisfaction and overall mental health [7].
• Morphine dependence in human neuroblastoma SH-SY5Y cells is associated with adaptive changes in both the quantity and functional interaction of PGE1 receptors and stimulatory G proteins [8].

High impact information on alprostadil

• Unlike the agents above, 8-Br-cAMP or PGE1 has no significant effect on protein synthesis, but does induce a small increase in S6 phosphorylation [9].
• PGE1 also inhibits platelet aggregation, probably through activation of platelet AC [10].
• The primary prostaglandins exert opposite effects to their own endoperoxide precursors, thus, PGE2 and PGE3 contract, and PGE1 relaxes the bovine coronary arteries [11].
• Secretion by MBP and EPO was inhibited by 1 microM PGE1, but the nature of the inhibition differed from that observed with thrombin [12].
• IL-10 also inhibited PGE1- and PGE2-induced IL-6 production [13].

Chemical compound and disease context of alprostadil

• To explore the mechanisms underlying prostaglandin E1 (PGE1)-associated immunosuppression in autoimmunity, we treated SJL mice immunized to produce immune-mediated interstitial nephritis with PGE1, PGF2 alpha, or vehicle alone [2].
• The action of prostacyclin, prostaglandin E1 (PGE1), and their mimetics on myocardial function includes changes in contractility, electrophysiological properties, and protection from injury caused by transient myocardial ischemia [14].
• Cyclic AMP (cAMP) is an intracellular second messenger that inhibits myeloid cell proliferation and is produced in myeloid leukemia cells on stimulation of adenylate cyclase enzyme by prostaglandin E1 (PGE1) [15].
• The effect of acetylcholine, 3,4-dihydroxyphenylethylamine, prostaglandin (PGE1), guanosine triphosphate (GTP), and divalent ions on adenylate cyclase activity in homogenates of ""differentiated" and malignant mouse neuroblastoma cells was studied [16].
• Adenylate cyclase responses to pituitary hormones including adrenocorticotropic hormone (ACTH), biogenetic amines, prostaglandin E1 (PGE1), angiotensin II, and glucagon were evaluated in adrenocortical tumors and hyperplastic adrenal tissues, obtained from patients with Cushing's syndrome at surgery, and in normal adrenals [17].

Biological context of alprostadil

• However, PGE1 had no effect on protein synthesis or S6 phosphorylation [18].
• Neutrophils harvested from the blood of rats treated with PGE1 show depressed responsiveness in chemotaxis and in enzyme secretion after incubation with chemotactic peptide [19].
• Maximal secretin activation was not additive to that of PGE1, suggesting a coupling to the same adenylyl cyclase catalytic site [20].
• The influence of PGE1 (0.9 mug per kg per min) on glucose, fluid, and ion transport was entirely reproducible throughout a 6-hr perfusion experiment and was fully reversible 60 min after the end of PGE1 administration [21].
• During infusion of PGE1, arterial blood pressure and respiratory activity should be monitored carefully and appropriate supportive steps taken if hypotension or respiratory depression occurs [4].

Anatomical context of alprostadil

• In our experiments, PGE1 or PGE2 suppressed the generation of cytotoxic T-lymphocytes in the syngeneic mixed lymphocyte tumor cell cultures [22].
• The observed immunosuppression is critically dependent on PGE1 administration during the period of effector T cell induction [2].
• PGE1 inhibits effector T cell induction in a dose-dependent, reversible manner, but has no inhibitory effect on fully differentiated DTH effector cells or SRTA-reactive cell lines [2].
• Perfusion studies were performed in 35 healthy volunteers to investigate further the secretory effect of prostaglandin E1 (PGE1), administered intraluminally, on the human jejunum [21].
• CONCLUSIONS: Long-term PGE1 administration was cytoprotective for both the liver and gastric mucosa in cirrhotic rats [23].

Associations of alprostadil with other chemical compounds

• Alterations in differentiation (tyrosinase activity) were determined in cells exposed to either melanocyte-stimulating hormone (MSH, 10(-7) M), theophylline (10(-3) M), N6,O2'-dibutyryl cyclic AMP (db-cAMP, 10(-4) M), or prostaglandin E1 (PGE1, 10(-6) M) [24].
• Hepatic and gastric leukotriene B4, myeloperoxidase and collagen levels were significantly lower in the PGE1-treated compared with vehicle-treated cirrhotic rats [23].
• During this delay myoblast fusion could be induced by prostaglandin E1 (PGE1), by raising extracellular potassium and by addition of carbachol [25].
• An increase in the rate of entry into S phase also occurred when PGE1 or PGE2 was added 8 or 15 hr after addition of PGF2 alpha [26].
• The altered response in DS fibroblasts was specific for beta-adrenergic agonists, because treatment of DS or control cells with PGE1 or cholera toxin resulted in the same degree of cyclic AMP accumulation [27].

Gene context of alprostadil

• In inside-out membrane vesicles derived from insect cells or HEK293 cells, MRP4 catalyzed the time- and ATP-dependent uptake of prostaglandin E1 (PGE1) and PGE2 [28].
• The JAK2 inhibitor AG490 blocked phosphorylation of STAT5 and PRL-induced, but not PGE1-induced, Cl- transport [29].
• Exposure of GH3 cells preloaded with 45Ca to TRH, PGE1, EGF, PMA, or VIP resulted in losses of cell-associated 45Ca [30].
• Reb suppressed PGE1 -, but not 15d-PGJ2-, induced increase of IL-6 and IL-8 production [31].
• The potent effects of alprostadil on endothelial VEGF and eNOS synthesis may be useful for patients with HF where endothelial dysfunction is involved in the disease process [32].

Analytical, diagnostic and therapeutic context of alprostadil

• The PGE1 derivative is considerably more effective than PGE1 and shows potent anti-inflammatory activity even after oral administration [19].
• BACKGROUND & AIMS: Prostaglandin E1 (PGE1) has been used after orthotopic liver transplantation (OLT) based on limited clinical data suggesting PGE1 infusion improves immediate hepatic allograft function [33].
• METHODS: One hundred eighteen patients were randomized to receive either PGE1 or crystalloid placebo intravenously after allograft revascularization [33].
• Initial intensive care unit stay was shorter in patients treated with PGE1 (4.0 +/- 3.6 days) compared with controls (10.5 +/- 17.1 days) (P < 0.01) [33].
• METHODS AND RESULTS: Twenty-one open-chest dogs were randomized to receive a 10-minute intravenous infusion of either liposome diluent (placebo), free PGE1 (2 micrograms/kg), or TLC C-53 (2 micrograms/kg PGE1) after 2 hours of left anterior descending (LAD) occlusion just before reperfusion [34].

References