Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostaglandin E2 has been reported both to stimulate glycogen-phosphorylase activity (glycogenolytic effect) and to inhibit the glucagon-stimulated glycogen-phosphorylase activity (antiglycogenolytic effect) in rat hepatocytes. It was the purpose of this study to resolve this apparent contradiction and to characterize the signalling pathways and receptor subtypes involved in the opposing prostaglandin E2 actions. Prostaglandin E2 (10 microM) increased glucose output, glycogen-phosphorylase activity and inositol trisphosphate formation in hepatocyte cell culture and/or suspension. In the same systems, prostaglandin E2 decreased the glucagon-stimulated (1 nM) glycogen-phosphorylase activity and cAMP formation. The signalling pathway leading to the glycogenolytic effect of PGE2 was interrupted by incubation of the hepatocytes with 4 beta-phorbol 12-myristate 13-acetate (100 nM) for 10 min, while the antiglycogenolytic effect of prostaglandin E2 was not attenuated. The signalling pathway leading to the antiglycogenolytic effect of prostaglandin E2 was interrupted by an incubation of cultured hepatocytes with pertussis toxin (100 ng/ml) for 18 h, whereas the glycogenolytic effect of prostaglandin E2 was enhanced. The EP1/EP3 prostaglandin-E2-receptor-specific prostaglandin E2 analogue Sulproston had a stronger glycogenolytic potency than the EP3 prostaglandin-E2-receptor-specific prostaglandin E2 analogue Misoprostol. The antiglycogenolytic potency of both agonists was equal. It is concluded that the glycogenolytic and the antiglycogenolytic effects of prostaglandin E2 are mediated via different signalling pathways in hepatocytes possibly involving EP1 and EP3 prostaglandin E2 receptors, respectively.
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PMID:Glycogenolytic and antiglycogenolytic prostaglandin E2 actions in rat hepatocytes are mediated via different signalling pathways. 828 25

Prostaglandins (PGs) exert their effects via binding to specific cell surface receptors and influencing second messenger systems through G-proteins. PGE2 may interact with at least four receptor subtypes (EP1, EP2, EP3, EP4), each showing different pharmacological profiles. The second messengers calcium, inositol phosphates (InsPs) and cyclic nucleotides play decisive roles in uterine contractility. The question in this investigation was, which EP receptors, G-proteins and second messenger systems transmit PGE2 induced signals in human myometrium. We have measured changes in InsPs and cAMP formation and also in intracellular calcium concentration ([Ca2+]i) induced by PGE2 and receptor subtype selective analogues in cultured human myometrial cells. PGE2 increased cAMP level and this effect was shared by the EP2 receptor subtype selective agonist Butaprost and by Misoprostol (EP3 > EP2 > EP1). Sulprostone (EP3 > EP1) did not stimulate adenylyl cyclase activity per se, but inhibited forskolin-stimulated adenylyl cyclase in a pertussis toxin (PT) sensitive way. PGE2, GR63799X (EP3 selective), Sulprostone and Misoprostol activated phospholipase-C (PLC), this effect was resistant to PT treatment. PGE2 also elevated [Ca2+]i from the resting level of 60-90 nM up to 350 nM. Low concentrations (1-300 nM) of PGE2 increased [Ca2+]i without PLC activation. The selective EP1 inhibitor AH6809, Nifedipine, Verapamil and PT treatment inhibited this effect of PGE2. In cultured human myometrial cells PGE2 interacts with EP1 receptors, which elevate [Ca2+]i independently from PLC, but involving a Gi protein and plasmamembrane calcium channels; EP2 receptors which stimulate adenylyl cyclase; EP3A receptors, which inhibit adenylyl cyclase activity through Gi activation and EP3D receptors which activate PLC through a PT-insensitive pathway and also elevate [Ca2+]i.
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PMID:Prostaglandin E receptors in myometrial cells. 953 Apr 35

Previous work has suggested that functional interrelationships may exist between inhibition of insulin secretion by interleukin (IL)-1beta and the endogenous synthesis of prostaglandin E(2) (PGE(2)) in the pancreatic islet. These studies were performed to ascertain the relative abundance of E prostaglandin (EP) receptor mRNAs in tissues that are major targets, or major degradative sites, of insulin; to identify which EP receptor type mediates PGE(2) inhibition of insulin secretion in pancreatic islets; and to examine possible sites of action through which sodium salicylate might affect IL-1beta/PGE(2) interactions. Real-time fluorescence-based RT-PCR indicated that EP3 is the most abundant EP receptor type in islets, liver, kidney, and epididymal fat. EP3 mRNA is the least, whereas EP2 mRNA is the most, abundant type in skeletal muscle. Misoprostol, an EP3 agonist, inhibited glucose-induced insulin secretion from islets, an event that was prevented by preincubation with pertussis toxin, by decreasing cAMP. Electromobility shift assays demonstrated that sodium salicylate inhibits IL-1beta-induced nuclear factor-kappaB (NF-kappaB) activation. Sodium salicylate also prevented IL-1beta from inducing EP3 and cyclooxygenase (COX)-2 gene expression in islets and thereby prevented IL-1beta from inhibiting glucose-induced insulin secretion. These findings indicate that the sites of action through which sodium salicylate inhibits these negative effects of IL-1beta on beta-cell function include activation of NF-kappaB as well as generation of PGE(2) by COX-2.
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PMID:Inhibition of interleukin-1beta-induced COX-2 and EP3 gene expression by sodium salicylate enhances pancreatic islet beta-cell function. 1203 64