Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To identify possible ligands of the orphan somatostatin-like receptor 1 (SLC-1), rat brain extracts were analyzed by using the functional expression system of Xenopus oocytes injected with cRNAs encoding SLC-1 and G protein-gated inwardly rectifying potassium channels (GIRK). A strong inward current was observed with crude rat brain extracts which upon further purification by cation exchange chromatography and high performance liquid chromatography (HPLC) yielded two peptides with a high agonist activity. Mass spectrometry and partial peptide sequencing revealed that one peptide is identical with the neuropeptide melanin concentrating hormone (MCH), the other represents a truncated version of MCH lacking the three N-terminal amino acid residues. Xenopus oocytes expressing the MCH receptor responded to nM concentrations of synthetic MCH not only by the activation of GIRK-mediated currents but also by the induction of Ca(2+) dependent chloride currents mediated by phospholipase C. This indicates that the MCH receptor can couple either to the G(i)- or G(q)-mediated signal transduction pathway, suggesting that MCH may serve for a number of distinct brain functions including food uptake behavior.
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PMID:Identification of melanin concentrating hormone (MCH) as the natural ligand for the orphan somatostatin-like receptor 1 (SLC-1). 1047 41

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that plays a key role in energy homeostasis. Like many neuropeptides, it signals through two G protein-coupled receptors. MCH receptor 1 (MCHR1) is the sole receptor expressed in rodents and couples to G(i) and G(q) proteins. Little is known about the intracellular pathways engaged by MCH and its receptor. Using HEK293 cells stably expressing MCHR1, we demonstrate that MCH, acting through MCHR1, antagonizes the action of forskolin, an adenylate cyclase activator that increases intracellular levels of cAMP. MCH also inhibits cAMP induction by the G(s)-coupled beta-adrenergic receptor. Activation of either the G(i)- or G(s)-dependent pathway typically results in ERK phosphorylation in HEK293 cells. In contrast to opposing actions on cAMP synthesis, simultaneous MCH and forskolin treatment results in synergistic activation of ERK. This synergy proceeds through pertussis toxin-independent pathways and requires several enzymatic activities such as protein kinase A, protein kinase C, phospholipase C, and Src kinase. Finally, we provide evidence that such positive interactions are not limited to cell lines but can also be observed in the brain.
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PMID:Melanin-concentrating hormone receptor 1 activates extracellular signal-regulated kinase and synergizes with G(s)-coupled pathways. 1286 33

Adipose tissue develops from differentiating preadipocytes that expand and migrate. 3T3-L1 preadipocytes respond to melanin-concentrating hormone (MCH) by increasing leptin production. Here, we investigate whether MCH elicits remodeling of the actin cytoskeleton and whether this translates into altered migratory capacity of these cells. Incubation with MCH resulted in a loss of actin stress fibers accompanied by a change in morphology from a stretched-out fibroblast to a rounded cell. PMC-3881-PI, a MCH receptor 1 antagonist blocked the effect, confirming this receptor is solely responsible for MCH-mediated actin rearrangements. Both a pharmacological activator and inhibitor of phospholipase C were used to demonstrate this molecule's importance to the signaling pathway. Finally, MCH was shown to facilitate preadipocyte migration into a scratch wound, revealing a previously unknown role for MCH in the regulation of cellular migration. We conclude that MCH could influence the expansion of adipose tissue through its ability to enhance preadipocyte migration.
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PMID:Melanin-concentrating hormone facilitates migration of preadipocytes. 2017 Dec 60