Intracellular signaling cAMP levels

The majority of GPCRs couple to three families of G protein alpha subunits which differ in their ability to activate three distinct primary signaling cascades. The stimulatory G-protein Gas, positively regulates the activity of adenylyl cyclase causing an increase of intracellular cAMP levels as second messenger. In... 

Parathyroid hormone (PTH) regulates calcium levels in blood and bone remodeling. The activation domain of that 84-amino acid polypeptide locates around the N-terminal (1-34 amino acids). Parathyroid hormone receptor is a typical G-protein coupled receptor, which is coupled to both adenyl cyclase/cAMP and PLCy/IP3/cytosolic Ca2+ intracellular signaling pathways. In order to identify the structural elements involved in the peptide hormone binding and signal initiation, Chorev et al. employed a photoaffinity scanning approach. The N-terminal amino acids were successively deleted or modified and the new N-terminus was replaced for photoreactive Bpa. The most active peptide ana-... 

On the other hand, a2-adrenoreceptors mostly mediate their intracellular signalling through G,. In this case, the signalling through the Ga and Gpy subunits may be important. Activation of the Gm leads to the inhibition of adenylyl cyclase (AC) with a reduction in cAMP levels, whereas activation of Gpy leads to inhibition of Ca2+ channels and activation of K+ channels and mitogen-activated protein kinases MAPK (Hein et al., 2006). 

Following cannabinoid binding, multiple signaling pathways can be activated Gij0jS-protein mediated modulation of adenylate cyclase and cAMP levels Ca2+ and K+ ion channel activation or activation of different intracellular enzymes/effectors (i.e., kinases, ceramide) in a non-G-protein dependent manner (Childers et al., 1993 Felder et al., 1995 Mackie et al., 1995 Prather et al., 2000 Sanchez et al., 2001). 

Opioid receptors are seven transmembrane G-protein coupled inhibitory receptors (Bockaert, 1991), although an association to excitatory G-proteins has also been reported (Varga et al., 2003). Intracellular signaling by these receptors involves the inhibition of adenylate cyclase with a subsequent decrease in cAMP levels (Surprenant et al., 1990), regulation of intracellular calcium levels, modulation of potassium channels (Williams et al., 2001), and control of MAP-kinase and ERK activity (Eitan et al., 2003 Varga et al., 2003). 

As observed with the other D2-like receptors, the D4 receptors mediate additional signaling events that are independent of the changes in cAMP levels. Some of these intracellular signals can be transduced by the Gpy complex. This is probably the case in HEK 293 transfected with a Gpy-sensitive adenylyl cyclase (ACII), in which activation of D4 receptor paradoxically produced a stimulation of cAMP production (Watts and Neve,... 

Although chemokines act through specific GPCRs, chemokines relate to cytokines through many overlapping intracellular signaling pathways. One of the first signaling pathways identified was the inhibition of adenylyl cyclase activity to reduce the intracellular cAMP levels, modulated by the Ga subunit of the Gi/o proteins (Damaj et al., 1996). It was also... 

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