Gq protein

FIGURE 2.7 Production of second messengers inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG) through activation of the enzyme phospholipase C. This enzyme is activated by the a- subunit of Gq-protein and also by Py subunits of Gj-protein. IP3 stimulates the release of Ca2+ from intracellular stores while DAG is a potent activator of protein kinase C. 

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. 

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 ). 

Phospholipases of type CP are activated by Gq proteins which conmumicate themselves with various 7-hehx transmembrane receptors. The initiating external signals are diverse (see Fig. 5.14) and include hormones, neurohormones and sensory signals such as odorous agents and light (in non-vertebrates). 

Since Ahlquist first proposed the existence of two adrenoceptor subtypes, o and 3, in 1948, the number of receptors has considerably expanded and at present nine distinct adrenoceptor subtypes have been identified. There are two subtypes of the o receptor (ol and o2, with subfamiiies of each of these) and three subtypes of the 3 receptor, 31, (32 and 33. The adrenoceptors are G protein-coupied receptors, but second messenger and G protein iinkage differ between the subtypes, ol-Adrenoceptor activation increases phosphoiipase C via a Gq protein, resuiting in an eievation in intraceiiuiar Ca2+-a2- Adrenoceptors are coupied to a Gi protein and... 

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. 

By molecular cloning, five subtypes of G protein-coupled mAChR have been identified and are termed M1-M5 (Caulfield and Birdsall 1998 Wess 1996). Based on their coupling to specific groups of heterotrimeric G proteins, mAChR may be divided into two functional classes M2 and M4 receptors are preferentially coupled to G,/0 signal transduction pathways, whereas Mi, M3, and M5 subtypes activate Gq proteins and downstream effectors (Wess 1996). 

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. 

Fadool, D. A., Estey, S. J., and Ache, B. W., Evidence that a Gq-protein mediates excitatory odor transduction in lobster olfactory receptor neurons, Chem. Senses, 20, 489, 1995. 

The 5-HT2 family comprises three receptor types 5-HT2A, 5-HT2B, and 5-HT2C, which show a high sequence homology, the similarity between their transmembrane domains being above 70%. These receptors are positively coupled to phospholipase C and phospholipase A2 through the Gq-protein and their activation leads to cell excitation (see Chapters 12 and 13 for details). 

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. 

Possible coupling of Dl-type receptors with Gi/o and Gq protein... 

It has been reported that D1 receptor stimulation can induce an intracellular mobilization of Ca2+ via the interaction of D1 receptor with a novel protein, calcyon (Lezcano et al., 2000). By a two-hybrid screening in yeast, calcyon was shown to associate with the C-terminal tail of D1 and D5 receptor. Activation of PKC by various stimulants allowed calcyon to couple the D1 or possibly D5 receptors with Gq protein, rendering these receptors able to produce intracellular Ca2+ mobilization. Calcyon is expressed at higher levels in the cortex than in the striatum and the intracellular calcium release induced by D1/D5 receptor stimulation is detected in cortical and hippocampal neurons in culture, but not in striatal neurons (Lezcano and Bergson, 2002 Zelenin et al., 2002). 

---