Gq protein-coupled

Wang, L., and Proud, C. G. (2002a). Ras/Erk signaling is essential for activation of protein synthesis by Gq protein-coupled receptor agonists in adult cardiomyocytes. Circ. Res. 91, 821-829. 

Most of the known actions of Ang II are mediated by the AT receptor, a Gq protein-coupled receptor. Binding of Ang II to ATi receptors in vascular smooth muscle results in activation of phospholipase C and generation of inositol trisphosphate and diacylglycerol (see Chapter 2). These events, which occur within seconds, result in smooth muscle contraction. 

Since the orexin receptors are Gq protein-coupled (Alexander et al. 2006), one may assume that this also holds true for the presynaptic orexin receptor(s), but so far no data are available. Nonetheless, the six studies carried out in central nervous preparations permit some conclusions on the post-G protein mechanisms. In all instances, the orexins increased the frequency of spontaneous inhibitory or excitatory postsynaptic potentials or currents. The results differed, however, with respect to the influence of tetrodotoxin. In the medial and lateral hypothalamus (van den Pol et al. 1998 Li et al. 2002), dorsal vagal complex (Davis et al. 2003), and caudal nucleus tractus solitarii (Smith et al. 2002), orexins increased the frequency of the miniature potentials or currents also in the presence of tetrodotoxin, suggesting that they directly influenced the vesicle release machinery (references in italics in Table 5). On the other hand, in the prefrontal cortex (Lambe and Aghajanian 2003) and lat-erodorsal tegmentum (Burlet et al. 2002), the orexins did not retain their facilitatory effect in the presence of tetrodotoxin, suggesting an effect further upstream e.g., on Ca2+ and/or K+ channels. 

Arimoto T, Takeishi Y, Takashi H, Shishido T, Niizeki T, Koyama Y, Shiga R, Nozaki N, Nakajima O, Nishimaru K, Abe J-I, Endoh M, Walsh RA, Goto K, Kubota I. 2006. Cardiac specific overexpression of diacylglycerol kinase prevents Gq protein-coupled receptor agonist-induced cardiac hypertrophy in transgenic mice. Circulation 113 60-66. 

Gq protein-coupled phosphatidylinositol-Ca " " pathway. The binding of a hormone at a specific receptor site results in the activation of G-protein which, in turn, activates phospholipase C via Gga-OTP-protein. The action of phospholipase C on phosphatidylinositol 4,5-bisphosphate (PIP2) yields inositol trisphosphate (IP3) and diacylglycerol (DAG) which, along with phosphatidylserine (PS), activates protein kinase C. IP3 binds to receptors on SER, releasing Ca " which, in turn, activates another set of protein kinases. -I-, Activation. 

Voltage and G-protein-gated channels K ch and Km (6 helices) quite similar to Ky(s) and Ky(r), but which interact with Gi proteins coupled to M2 muscarinic acetylcholine receptors, or with Gq proteins coupled to M3 receptors, respectively. Stimulation of M2 or M3 muscarinic receptors by acetylcholine in pacemaker cardiac... 

The two subtypes of ct-adrenerglc receptors, ctj and ct2, are coupled to different G proteins. The ai-adrenerglc receptor is coupled to a Gj protein that inhibits adenylyl cyclase, the same effector enzyme associated with (3-adrenerglc receptors. In contrast, the Gq protein coupled to the a2 sdrenerglc receptor activates a different effector enzyme that generates different second messengers (see Section 13.5). 

We now know that endothelial cells contain a Gq protein-coupled receptor that binds acetylcholine and activates phospholipase C, leading to an Increase In the level of... 

The activation of the calcium second messenger system by hormones, neurotransmitters, iocal mediators, and sensory stimuii is very important in reguiating VSM contraction. Severai signai transduction mechanisms modulate intracellular calcium concentration and, therefore, the state of vascular tone. These calcium second messenger systems are the phosphatidyiinositol (PIP2)/Gq protein-coupled pathway, the cyclic adenosine monophosphate (cAMP)/Gs protein-coupied pathway, and the NO/cyclic guanosine monophosphate (cGMP) pathway. 

Weber B, Schlicker E. Modulation of dopamine release in the guinea-pig retina by Gi- but not by Gs- or Gq-protein-coupled receptors. Eundam. Clin. Pharmacol. 15, 393-400 (2001). 

Neuromedin U is a neuropeptide which is widely distributed in the gut and central nervous system. Peripheral activities of neuromedin U include stimulation of smooth muscle, increase in blood pressure, alteration of ion transport in the gut, control of local blood flow and regulation of adrenocortical function. The actions of neuromedin U are mediated by G-protein coupled receptors (NMU1, NMU2) which are coupled tO Gq/11. 

The 3 isozymes are activated by G protein-coupled receptors through two different mechanisms [2]. The first involves activated a-subunits of the Gq family of heterotrimeric G proteins (Gq, Gn, Gi4, G15/16). These subunits activate the (31, (33 and (34 PLC isozymes through direct interaction with a sequence in the C terminus. The domain on the Gqa-subunit that interacts with the (3 isozymes is located on a surface a-helix that is adjacent to the Switch III region, which undergoes a marked conformational change during activation. The second mechanism of G protein activation of PLC 3 isozymes involves (3y-subunits released from Gi/0 G proteins by their pertussis toxin-sensitive activation by certain receptors. The 3y-subunits activate the 32 and 33 PLC isozymes by interacting with a sequence between the conserved X and Y domains. 

Most GPCRs interact with and activate more than one G-protein subfamily, e.g., with Gs plus Gq/n (histamine H2, parathyroid hormone and calcitonin recqrtors), Gs plus G (luteinising hormone receptor, 32-adrenoceptor) or Gq/11 plus G12/13 (thromboxane A2, angiotensin ATb endothelin ETA receptors). Some receptors show even broader G-protein coupling, e.g., to Gi, Gq/n plus Gi n ( protease-activated receptors, lysophosphatidate and sphingosine-1-phosphate receptors) or even to all four G-protein subfamilies (thyrotropin receptor). This multiple coupling results in multiple signaling via different pathways and in a concerted reaction of the cell to the stimulus. 

Figure 3.1 Schematic representation of a generic excitatory synapse in the brain. The presynaptic terminal releases the transmitter glutamate by fusion of transmitter vesicles with the nerve terminal membrane. Glutamate diffuses rapidly across the synaptic cleft to bind to and activate AMPA and NMDA receptors. In addition, glutamate may bind to metabotropic G-protein-coupled glutamate receptors located perisynaptically to cause initiation of intracellular signalling via the G-protein, Gq, to activate the enzyme phospholipase and hence produce inositol triphosphate (IP3) which can release Ca from intracellular calcium stores...

Histamine acts on four G-protein-coupled receptors, three of which are clearly important in the brain 256 H, receptors are intronless GPCRs linked to Gq and calcium mobilization 256... 

Metabotropic receptors (right half of the table) are coupled to G proteins (see p. 386), through which they influence the synthesis of second messengers. Receptors that work with type Gj proteins (see p. 386) increase the cAMP level in the postsynaptic cell ([cAMP] I), while those that activate Gj proteins reduce it ([cAMP] i ). Via type Gq proteins, other receptors increase the intracellular Ca "" concentration ([Ca j ). 

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