Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the effects of prostaglandin (EP) receptor subtype agonists on DNA synthesis and proliferation in primary cultures of adult rat hepatocytes to elucidate their mechanisms of action. Maintained in short-term cultures (i.e. 3.5 h) in a serum-free, defined medium, hepatocyte parenchymal cells underwent DNA synthesis and proliferation in the presence of sulprostone (10(-6) M), PGE(2) (10(-6) M), and 17-phenyl-trinor-PGE(2) (10(-9) M) in a time- and dose-dependent manner. PGE(2) was less potent than 17-phenyl-trinor-PGE(2) in stimulating hepatocyte mitogenesis. Sulprostone (10(-6) M) and 11-deoxy-PGE(1) (10(-6) M) showed weak and insignificant stimulation, respectively, for hepatocyte mitogenesis. These effects of PGE(2), 17-phenyl-trinor-PGE(2), and sulprostone were abolished by treatment with a specific EP(1) receptor antagonist, SC-51322, or the PLC inhibitor U-73122. The effects of these EP(1) receptor agonists were potentiated by ionomycin and blocked by verapamil. Hepatocyte mitogenesis was almost completely blocked by specific inhibitors of growth-related signal transducers, such as genistein, wortmannin, PD98059, and rapamycin. A monoclonal antibody against TGF-alpha dose-dependently inhibited PGE(2)- and 17-phenyl-trinor-PGE(2)-induced hepatocyte mitogenesis. Treatment with the EP(1) receptor agonists significantly increased the secretion of TGF-alpha, reaching a maximum within 5 min. The increase in TGF-alpha secretion was blocked by SC-51322, U-73122, somatostatin, and verapamil and potentiated by ionomycin. These results indicate that the proliferative mechanisms of action of EP(1) receptor agonists are mediated through an increase in the autocrine secretion of TGF-alpha, which is dependent on the EP(1) receptor/G-protein involved in PLC regulation/PLC/Ca(2+) system. The locally secreted TGF-alpha, in turn, acts as a complete mitogen that stimulates the tyrosine kinase/MAPK pathway in these cells.
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PMID:Prostaglandin E(2) (EP(1)) receptor agonist-induced DNA synthesis and proliferation in primary cultures of adult rat hepatocytes: the involvement of TGF-alpha. 1156 7

(1) Peripheral inflammation causes an increase in the proportion of primary afferent neurones that express neurokinin(1) (NK(1)) receptors for substance P (SP). This upregulation may contribute to the neuronal mechanisms of inflammatory pain. The aim of this study was to identify endogenous mediators that stimulate upregulation of NK(1) receptors in dorsal root ganglion (DRG) neurones. Cultured DRG neurones from the adult normal rat were exposed for 2 days to media that contained specific mediators, namely potassium in high concentration, prostaglandin E(2) (PGE(2)), somatostatin (SRIF), and compounds influencing second messenger cascades. After fixation neurones were labelled with an NK(1) receptor antibody. (2) Repetitive addition of the inflammatory mediator PGE(2) or dibutyryl-cyclic adenosine 3',5' monophophate (db-cAMP) to the culture medium enhanced the proportion of neurones with NK(1) receptor-like immunoreactivity from about 12% up to 40%. PGE(2)-induced upregulation was prevented by coadministration of PGE(2) and a protein kinase A inhibitor or SRIF to the medium. High potassium concentration, protein kinase C inhibitors and omission of nerve growth factor from the medium had no effect. (3) In calcium-imaging experiments, bath application of SP evoked increases of the intracellular calcium concentration in about 20% of the neurones. This proportion increased to about 40% after PGE(2)-pretreatment, but the increase was prevented when PGE(2) and SRIF were coadministered to the medium. (4) These data show that the expression of NK(1) receptor-like immunoreactivity in DRG neurones is regulated by the inflammatory mediator PGE(2). This upregulation depends on the intracellular adenylyl cyclase-protein kinase A pathway.
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PMID:Prostaglandin E2 increases the expression of the neurokinin1 receptor in adult sensory neurones in culture: a novel role of prostaglandins. 1278 27

Here we compared the effects of cortistatin and somatostatin on the production of prostanoids from primary cultures of rat cortical microglia and astrocytes. We found that both cortistatin and somatostatin do not modify basal PGE(2) release from cultured astrocytes in 24-h experiments. Somatostatin further enhanced the increase in PGE(2) release induced by IL-1beta, whereas cortistatin inhibited such increase. Experiments on microglia showed that somatostatin has no effect on basal and IL-1beta-stimulated PGE(2) release, whereas cortistatin reduced baseline prostanoids production and abolished stimulation elicited by IL-1beta. The latter effect was associated to the inhibition of COX-2 gene over-expression induced by the cytokine.
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PMID:Diverging effects of cortistatin and somatostatin on the production and release of prostanoids from rat cortical microglia and astrocytes. 1955 66


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