Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The diverse physiological actions of somatostatin are mediated by a family of G-protein coupled receptors (SSTRs). Several peptide analogues of somatostatin such as octreotide have been developed for therapeutic use, including treatment of gastrointestinal disorders such as secretory diarrhoea. However, their development as anti-diarrhoeal agents has been limited by poor oral bioavailability, necessitating parenteral administration. This in vitro study investigated the anti-secretory potential of a group of novel, non-peptide, somatostatin-receptor agonists that selectively activate specific SSTR subtypes to assess their potential for oral administration. 2. The ability of the agonists to inhibit forskolin-stimulated chloride secretion was measured using a sensitive bioassay system in isolated rat colonic mucosa. 3. The SSTR-2 selective agonist, L-779,976 was 10-times more potent than octreotide as an inhibitor of secretion when added to the basolateral surface of rat colon. Non-peptide agonists selective for SSTR1 (L-797,591), SSTR3 (L-796,778), SSTR4 (L-803,087) or SSTR5 (L-817,818) showed little or no anti-secretory activity in this preparation. 4. L-779,976 was able to inhibit secretion when applied to the luminal surface at sub-micromolar concentrations suggesting that it can cross the colonic epithelium. The anti-secretory potency of luminal L-779,976 was increased 3 fold in the presence of GF120918, a known inhibitor of P-glycoprotein. 5. Non-peptide somatostatin receptor agonists may provide a basis for the development of new, orally available anti-diarrhoeal therapies.
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PMID:Anti-secretory properties of non-peptide somatostatin receptor agonists in isolated rat colon: luminal activity and possible interaction with P-glycoprotein. 1190 57

To examine the effect and the molecular mechanisms of the combined treatment of the somatostatin (SST) analogue octreotide with docetaxel: analysis of proliferation, apoptosis and migration in the human prostate cancer cell line PC3, either sensitive (PC3wt) or made resistant to docetaxel (PC3R). We examined the effect of the two drugs individually or in combination on cell proliferation and migration by analysis of apoptosis and cell cycle proteins. The role of octreotide in modulating P-glycoprotein function was examined together with the modulation of SST receptors type 2 and 5 (SSTR2 and SSTR5). We observed an enhanced effect of docetaxel and octreotide given in combination or in sequence compared with either agent alone; this result was particularly evident when docetaxel was given before octreotide in PC3wt and when the two drugs were given together in PC3R cells. In contrast to lanreotide, our data indicate that octreotide does not act as a P-glycoprotein inhibitor in PC3R cells. A role of docetaxel and combined treatment in regulating SSTR2, SSTR5, proliferation and apoptosis gene expression is suggested as the possible mechanism for the enhanced effect observed. In addition, an evaluation of the effect of the combined treatment on cellular migration was examined, showing a moderate loss of invasive properties in PC3R cells. The present results confirm that SST analogues may be combined with docetaxel to increase the antitumour effect in patients with advanced prostate carcinoma.
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PMID:Differential molecular mechanism of docetaxel-octreotide combined treatment according to the docetaxel-resistance status in PC3 prostate cancer cells. 2299 Jan 29