Disease relevance of Seglitide acetate

• The effects of MK 678 were reversible and blocked by pertussis toxin pretreatment, suggesting that SSTR2 couples to the L-type Ca2+ channels via G proteins [1].

Psychiatry related information on Seglitide acetate

• Furthermore, MK 678, when applied to the nucleus accumbens, evokes locomotor activity, and SRIF1 receptors in this brain region selectively mediate the stimulation of this behavioral response to SRIF [2].

High impact information on Seglitide acetate

• In contrast, the somatostatin analogs SMS 201-995, IM 4-28, and MK-678 failed to displace specific binding in transfected cells [3].
• Binding of the SST analogue MK 678 to the solubilized receptor was completely inhibited by guanosine 5'-O-thiotriphosphate (IC50 = 100 nM), reflecting decreased receptor affinity for agonist following uncoupling of the receptor and G protein(s) [4].
• Treatment of AtT-20 cells in culture with neuraminidase (V. cholera) greatly reduces high affinity [125I] MK 678 binding sites, but did not alter the maximal ability of SRIF to inhibit forskolin-stimulated cAMP accumulation in intact AtT-20 cells [5].
• The two receptors exhibited similar affinities for a number of SSTR2-selective agonists such as MK-678 [6].
• In contrast, the SSTR2 receptor was insensitive to CGP 23996-like compounds but bound MK 678 with high affinity [7].

Biological context of Seglitide acetate

• Blood pressure reduction in hypertensive-diabetic rats by the somatostatin analog MK-678 [8].
• These receptors exhibit high affinity for MK 678 throughout the period of cell multiplication [9].

Anatomical context of Seglitide acetate

• SRIF, MK 678, and CGP 23996 are able to inhibit forskolin-stimulated adenylate cyclase activity in rat neocortical membranes by 25-30% [10].
• The cortex, hippocampus and striatum also express SRIF2, or MK 678-insensitive, receptors [11].
• 2. Increasing concentrations SRIF or other SRIF receptor ligands inhibited specific [125I]-Tyr11-SRIF binding in CHOsst4 cell membranes with respective pIC50 values of SRIF (8.82), L-362855 (7.40), BIM-23027 (<5.5) and MK-678 (<5.5) [12].
• Somatostatin receptors in the intermediate zone of fetuses and in the cortical plate of postnatal rats exhibit high and low affinities respectively for the somatostatin analogue MK 678 [9].

Associations of Seglitide acetate with other chemical compounds

• Treatment of the receptor with endoglycosidase D did not affect the specific binding of [125I] MK 678 to the solubilized SRIF receptors, consistent with the finding from lectin affinity chromatography that high mannose-type carbohydrate structures were not associated with SRIF receptors [5].
• The binding of 125I-MK-678 to SRIF1 receptors was monophasically inhibited by SRIF, the octapeptides (such as SMS-201-995), and the hexapeptides (such as MK-678), consistent with the highly selective labeling of a subtype of SRIF receptor [13].
• Antagonist effects of seglitide (MK 678) at somatostatin receptors in guinea-pig isolated right atria [14].
• The sst(1) agonist L-797,591 (10(-5) M) mimicked the effect of CH-275, while MK-678 and L-803,087 at the same concentration were unable to influence somatostatin levels [15].
• In addition to SRIF-14 and SRIF-28, the most potent SRIF peptides were the cyclic octapeptides, BIM-23014C, BIM-23023, SMS 201-995, and the cyclic hexapeptides, MK-678 and BIM-23027 [16].

Gene context of Seglitide acetate

• The SSTR1 receptor could also bind CGP 23996-like compounds but not MK 678 [7].
• The inhibition by MK-678 was incomplete, indicating this peptide is highly selective for a subtype of SRIF receptor that we have termed the SRIF1 receptor [13].
• In experiments using in-gel kinase assays, MK-678 also inhibited EGF-stimulated ERK activity via a pertussis toxin sensitive pathway, and this effect resulted in inhibition of Elk-1 transcriptional activity [17].
• SRIF1 receptors have high affinity for MK 678, whereas SRIF2 receptors have no affinity for MK 678 but selectively bind peptides with structures similar to that of CGP 23996 [7].
• Subtypes of SRIF receptors are found in the CNS that are distinguished by their sensitivities to the cyclic hexapeptide MK-678, such that SRIF1 receptors are sensitive to MK-678 and SRIF2 receptors are insensitive to MK-678 [13].

References