Disease relevance of 16,16-Dimethyl-pge2

• The cytoprotective and acid-inhibitory effects of cimetidine and 16,16-dimethyl PGE2 were evaluated in a septic canine erosive gastritis model [1].
• These results suggest that 15-methyl PGE2 and 16,16-dimethyl PGE2 may be of value in the treatment of peptic ulcer [2].
• In 6 unoperated Zollinger-Ellison syndrome patients, 1 microgram/kg of oral 16,16-dimethyl PGE2 significantly inhibited fasting gastric acid hypersecretion by approximately 85% without significantly altering serum gastrin [3].
• 16,16-dimethyl-PGE2 protection against alpha-naphthylisothiocyanate-induced experimental cholangitis in the rat [4].
• The higher dose of 16,16-dimethyl-PGE2 (200 micrograms/kg body weight) caused a significant reduction in both PFC number and antibody titre compared with the control [5].

High impact information on 16,16-Dimethyl-pge2

• Cimetidine prevents the development of sepsis-induced gastric erosions by inhibition of acid secretion and 16,16-dimethyl PGE2 by cytoprotection [1].
• 0.1 microgram/kg of intravenous of 1 microgram/kg of oral 16,16-dimethyl PGE2 inhibited meal-stimulated acid secretion and gastrin by 80-90% [3].
• Stimulation of alkaline secretion in amphibian-isolated gastric mucosa by 16,16-dimethyl PGE2 and PGF2 alpha. A proposed explanation for some of the cytoprotective actions of prostaglandins [6].
• As previously reported, the physiologically active analogue 16,16-dimethyl-PGE2 inhibited glucagon-stimulated glycogenolysis [7].
• Epinephrine-stimulated glycogenolysis was inhibited by 16,16-dimethyl-PGE2 in a dose-dependent manner [7].

Chemical compound and disease context of 16,16-Dimethyl-pge2

• Gastrointestinal side effects, assessed by the antagonism of morphine-induced constipation in the mouse, were relatively low with some of these compounds, six of which had a much more favourable relative selectivity than 16,16-dimethyl-PGE2 methyl ester [8].
• When either 16,16-dimethyl PGE2 (30 ug/mouse) or Misoprostol (60 ug/mouse) was administered daily in vivo, there was a significant suppression of splenomegaly in F1 mice (C57Bl/6 x CBA) which had been injected with parental (C57Bl/6) spleen cells [9].
• Alloxan-induced hyperglycemia in rats is reduced by 16,16-dimethyl-PGE2 [10].

Biological context of 16,16-Dimethyl-pge2

• Modulation of the kinetics of the initial leukocyte migration into renal allografts by 16,16-dimethyl PGE2 [11].
• Effects of COX inhibitors on neutrophil infiltration, apoptosis, and TNF-alpha expression in H. pylori-infected mice were abolished by exogenous 16,16-dimethyl PGE2 [12].
• The effect of 140 mug of 16,16-dimethyl PGE2 on gastric emptying and intestinal transit of a barium-food mixture has been studied in 8 healthy male volunteers [13].
• The efficacy of 16,16 dimethyl PGE2 p-benzaldehyde semicarbazone ester for cervical dilatation prior to evacuation of the uterus in 180 first trimester nulliparae has been studied [14].
• Cervical dilatation with 16,16 dimethyl PGE2 p-benzaldehyde semicarbazone ester prior to vacuum aspiration in first trimester nulliparae [14].

Anatomical context of 16,16-Dimethyl-pge2

• All doses of 16,16-dimethyl PGE2, between 0.01 and 0.1 microgram/kg i.v. and between 0.01 and 1.0 microgram/kg orally produced significant postprandial inhibitory effects on both gastric acid secretion and gastrin release as compared with saline control [3].
• 1. Prostanoid receptors have been characterized in a range of guinea-pig and rat smooth muscle and platelets, according to the scheme of Coleman et al., (1985a), using agonists (prostaglandin D2 (PGD2), PGE1, PGE2, 16,16 dimethyl PGE2, PGF2 alpha, PGI2 and U46619) and putative selective antagonists (AH 6809 and SQ 29,548) [15].
• 2. Prostaglandin (PG) E2, PGF2 alpha and 16,16-dimethyl-PGE2 did not stimulate fibrinogen synthesis and fibrinogen polypeptide mRNA content when administered intraperitoneally to rats or when added to monolayer cultures of rat hepatocytes [16].
• Intravenous injection of chicks with bovine parathyroid hormone (1-34) (3.3 micrograms/100 g body wt.) or 16,16-dimethyl PGE2 (5 micrograms/100 g body wt.) caused rapid (3 minute) net inhibition of 45Ca uptake into femur and calvarium [17].
• 16,16-Dimethyl-PGE2 significantly increased the volume of gastric juice and mucus thickness [18].

Associations of 16,16-Dimethyl-pge2 with other chemical compounds

• In contrast, glycogenolysis stimulated by N6,O2'-dibutyryladenosine-3',5'-cyclic monophosphate (dibutyryl-cAMP) was unaffected by either PGE2 or 16,16-dimethyl-PGE2 (rate of glycogenolysis with 0.34 microM dibutyryl-cAMP plus 1.7 microM 16,16-dimethyl-PGE2 = 99 +/- 6% of rate with 0.34 microM dibutyryl-cAMP alone; mean +/- SEM, N = 5) [7].
• The stable prostaglandin E2 analogue, 16,16-dimethyl PGE2 (di-M-PGE2) was continuously infused by osmotic pump directly into rat heterotopic cardiac allografts [19].
• 15(R)-methyl PGE2 methyl ester (15MPG) and 16,16-dimethyl PGE2 methyl ester (16DMPG) were assessed for their effect on gastric mucosal permeability to Na+ and H+ in dogs prepared by antrectomy and vagally-denervated fundic pouches [20].
• These results confirm and extend a previous report that 16,16-dimethyl PGE2 increased thymidine uptake in the duodenum but not the stomach [21].
• When rats pretreated with indomethacin were injected with a cytoprotective dose of 16,16-dimethyl-PGE2, there was an increase in fluorescence of the gastric perfusate treated with ANS, suggesting that hydrophobic factors, perhaps lipids, were being secreted in association with mucus [22].

Gene context of 16,16-Dimethyl-pge2

• COX-2 inhibitors or dexamethasone aggravate ischemia-reperfusion-induced mucosal damage up to 4-fold, an effect abolished by concurrent administration of 16,16-dimethyl-PGE2 [23].
• TNFR1-/- mice were radioprotected by administration of exogenous 16,16-dimethyl PGE2 [24].
• 16,16-dimethyl-PGE2 and two putative EP1 antagonists, AH6809 and SC-19220, did not show any significant binding to this receptor [25].
• The effects of 16,16-dimethyl PGE2 and phosphodiesterase inhibitors on Con A blastogenic responses and NK cytotoxic activity of mouse spleen cells [26].
• On human and ferret airway smooth muscle it abolished contractions induced by PGD2, PGF2 alpha and 16,16-dimethyl-PGE2 [27].

Analytical, diagnostic and therapeutic context of 16,16-Dimethyl-pge2

• Since 16,16-dimethyl PGE2, whether given orally or intravenously, is a potent inhibitor of both gastric acid secretion and meal-stimulated gastrin release, without apparent untoward side effects, clinical trials with 16,16-dimethyl PGE2 are indicated in patients with acid peptic disease [3].
• Fasted rats were given either 16,16-dimethyl-PGE2 (dmPGE2) (1 microgram/kg) or normal saline subcutaneously followed by the oral administration of 1 ml of 100% ethanol or saline 30 min later [28].
• These responses were completely abolished by bilateral vagotomy or atropine, while 16,16-dimethyl PGE2 decreased the mucosal ulcerogenic response with no effect on acid secretion [29].

References