Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.17 (CaMKII)
 4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropeptide Y (NPY) has at least three receptors (Y1, Y2, and Y3) through which it influences different mechanisms in many cell types. Previous data suggest that the Y2 receptor may be divided into prejunctional and postjunctional subgroups. We have examined the intracellular signalling pathways of the postjunctional Y2 receptor in rat renal proximal tubules. The results indicate that NPY regulates Na+,K(+)-ATPase through several signalling pathways: (1) In proximal tubule (PT) cells NPY increased intracellular calcium. The response was blocked by removing extracellular calcium and was also blocked by using nifedipine. This suggests that calcium was increased by influx from the extracellular space through L-type calcium channels. (2) NPY increased Na+,K(+)-ATPase activity in PT segments and this effect was also blocked by nifedipine. CaMKII-Ala286[281-302] a blocker of Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibited the NPY-stimulated Na+,K(+)-ATPase activity. This implies that increased intracellular calcium activates CaMKII which subsequently increases Na+,K(+)-ATPase activity. CaMKII thus appear to act similar to what has been proposed for protein phosphatase 2B. (3) Calphostin C, an inhibitor of protein kinase C (PKC), did not inhibit NPY-stimulated Na+,K(+)-ATPase activity. PKC is, therefore, unlikely to be involved. (4) Y2 receptors are negatively coupled to the cAMP pathway. NPY attenuated forskolin-stimulated cAMP production in renal tubules and exogenous cAMP counteracted the NPY-stimulated Na+,K(+)-ATPase activity. This illustrated the importance of NPY for the regulation of renal sodium handling. We also propose that the renal tubule cell is a good model for studying the function and mechanisms of postjunctional Y2 receptors.
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PMID:Neuropeptide Y regulates rat renal tubular Na,K-ATPase through several signalling pathways. 887 53

The amygdala modulates memory consolidation with the storage of emotionally relevant information and plays a critical role in fear and anxiety. We examined changes in neuronal morphology and neurotransmitter content in the amygdala of rats exposed to a single prolonged stress (SPS) as a putative animal model for human post-traumatic stress disorder (PTSD). Rats were perfused 7 days after SPS, and intracellular injections of Lucifer Yellow were administered to neurons of the basolateral (BLA) and central amygdala (CeA) to analyze morphological changes at the cellular level. A significant increase of dendritic arborization in BLA pyramidal neurons was observed, but there was no effect on CeA neurons. Neuropeptide Y (NPY) was abundant in BLA under normal conditions. The local concentration and number of immunoreactive fibers of NPY in the BLA of SPS-exposed rats were increased compared with the control. No differences were observed in this regard in the CeA. Double immunostaining by fluorescence and electron microscopy revealed that NPY immunoreactive terminals were closely associated with calcium/calmodulin II-dependent protein kinase (CaMKII: a marker for pyramidal neurons)-positive neurons in the BLA, which were immunopositive to glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). SPS had no significant effect on the expression of CaMKII and MR/GR expression in the BLA. Based on these findings, we suggest that changes in the morphology of pyramidal neurons in the BLA by SPS could be mediated through the enhancement of NPY functions, and this structural plasticity in the amygdala provides a cellular and molecular basis to understand for affective disorders.
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PMID:Effects of single-prolonged stress on neurons and their afferent inputs in the amygdala. 1830 74

Neuropeptide Y (NPY), a sympathetic cotransmitter, acts via G protein-coupled receptors to stimulate constriction and vascular smooth muscle cell (VSMC) proliferation through interactions with its Y1 receptors. However, VSMC proliferation appears bimodal, with high- and low-affinity peaks differentially blocked by antagonists of both Y1 and Y5 receptors. Here, we sought to determine the signaling mechanisms of NPY-mediated bimodal mitogenesis. In rat aortic VSMCs, NPY's mitogenic effect at all concentrations was blocked by pertussis toxin and was associated with decreased forskolin-stimulated cAMP levels. NPY also increased intracellular calcium levels; in contrast to mitogenesis, this effect was dose dependent. The rise in intracellular Ca2+ depended on extracellular Ca2+ and was mediated via activation of Y1 receptors, but not Y5 receptors. Despite differences in calcium, the signaling pathways activated at low and high NPY concentrations were similar. The mitogenic effect of the peptide at all doses was completely blocked by inhibitors of calcium/calmodulin-dependent kinase II (CaMKII), protein kinase C (PKC), and mitogen-activated protein kinase kinase, MEK1/2. Thus, in VSMCs, NPY-mediated mitogenesis signals primarily via Y1 receptors activating 2 Ca2+-dependent, growth-promoting pathways -- PKC and CaMKII. At the high-affinity peak, these 2 pathways are amplified by Y5 receptor-mediated, calcium-independent inhibition of the adenylyl cyclase - protein kinase A (PKA) pathway. All 3 mechanisms converge to the extracellular signal-regulated kinases (ERK1/2) signaling cascade and lead to VSMC proliferation.
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PMID:Interactions of multiple signaling pathways in neuropeptide Y-mediated bimodal vascular smooth muscle cell growth. 1864 93