Soluble adenylyl cyclase-mediated cAMP signaling and the putative role of PKA and EPAC in cerebral mitochondrial function.

Mitochondria produce the bulk of the ATP in most cells, including brain cells. Regulating this complex machinery to match the energetic needs of the cell is a complicated process that we have yet to understand in its entirety. In this context, 3',5'-cyclic AMP (cAMP) has been suggested to play a seminal role in signaling-metabolism coupling and regulation of mitochondrial ATP production.

The inhibitors of soluble adenylate cyclase 2-OHE, KH7, and bithionol compromise mitochondrial ATP production by distinct mechanisms.

Soluble adenylate cyclase (sAC) is a non-plasma membrane-bound isoform of the adenylate cyclases signaling via the canonical second messenger, 3',5'-cyclic AMP (cAMP). sAC is involved in key physiological processes such as insulin release, sperm motility, and energy metabolism. Thus, sAC has attracted interest as a putative drug target and attempts have been made to develop selective inhibitors.

The P2X7 receptor and pannexin-1 are involved in glucose-induced autocrine regulation in β-cells.

Extracellular ATP is an important short-range signaling molecule that promotes various physiological responses virtually in all cell types, including pancreatic β-cells. It is well documented that pancreatic β-cells release ATP through exocytosis of insulin granules upon glucose stimulation. We hypothesized that glucose might stimulate ATP release through other non-vesicular mechanisms.

Dynamic Changes in Cytosolic ATP Levels in Cultured Glutamatergic Neurons During NMDA-Induced Synaptic Activity Supported by Glucose or Lactate.

We have previously shown that synaptic transmission fails in cultured neurons in the presence of lactate as the sole substrate. Thus, to test the hypothesis that the failure of synaptic transmission is a consequence of insufficient energy supply, ATP levels were monitored employing the ATP biosensor Ateam1.03YEMK.

Primary cultures of astrocytes: their value in understanding astrocytes in health and disease.

During the past few decades of astrocyte research it has become increasingly clear that astrocytes have taken a central position in all central nervous system activities. Much of our new understanding of astrocytes has been derived from studies conducted with primary cultures of astrocytes. Such cultures have been an invaluable tool for studying roles of astrocytes in physiological and pathological states.

The pharmacological effect of positive KCNQ (Kv7) modulators on dopamine release from striatal slices.

Retigabine is an anti-epileptic drug that inhibits neuronal firing by stabilizing the membrane potential through positive modulation of voltage-dependent KCNQ potassium channels in cortical neurons and in mesencephalic dopamine (DA) neurons. The purpose of this study was to compare the effect of retigabine with other positive KCNQ modulators on the KCl-induced release of DA in rat striatal slices. Retigabine was found to inhibit KCl-dependent release of DA, and the IC(50) was estimated to be 0.