G proteins, second messenger

Cellular processes involving the classic ligand-receptor interaction and beyond (e.g., G-proteins, second messenger systems)... 

Receptor Type Endogenous Agonist G protein, Second Messenger Smooth Muscle Tone Result of Receptor Knockout... 

Receptor Location G Protein Second Messenger Major Functions... 

G-protein receptor systems are widespread in living systems. They are found in many animals and microbes. Both vision and smell in humans depend on G-proteins (Campbell et al., 1999), and glucagon receptors use the system to produce a second messenger called cyclic AMP (cAMP). Receptors for epinephrine, angiotensin, endorphins, and acetylcholine also use this G-protein second messenger mechanism (Sleight and Lieberman, 1995). 

Baclofen (Figure 89.12) is a presynaptic and postsyn-aptic GABA-B receptor agonist. When activated, a G protein second-messenger system stimulates opening of K channels, thereby hyperpolarizing the neuron [23,24). 

Two stages of amplification occur in the G-protein-mediated signal response. First, a single ligand-receptor complex can activate many G proteins. Second, the G-protein-activated adenylyl cyclase or phospholipase synthesizes many second messenger molecules. Some of these intracellular second messengers and their effects are given in Table 6.2. 

Ligand-gated ion channels) (G-coupled protein/second messenger)... 

Pseudohypoparathyroidism is characterized by end-organ resistance to parathyroid hormone (98,108). This disease takes various forms, including Albright s hereditary osteodystrophy, which has unusual physical features and a generalized resistance to G-protein-linked hormones that function through cAMP as a second messenger. This defect is associated with a deficiency in the levels of the a-subunit of (109). Because this defect may be generalized, such patients also have olfactory dysfunction (110). 

Excitation of smooth muscle via alpha-1 receptors (eg, in the utems, vascular smooth muscle) is accompanied by an increase in intraceUular-free calcium, possibly by stimulation of phosphoUpase C which accelerates the breakdown of polyphosphoinositides to form the second messengers inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 releases intracellular calcium, and DAG, by activation of protein kinase C, may also contribute to signal transduction. In addition, it is also thought that alpha-1 adrenergic receptors may be coupled to another second messenger, a pertussis toxin-sensitive G-protein that mediates the translocation of extracellular calcium. 

At a cellular level, the activation of mAChRs leads to a wide spectrum of biochemical and electrophysiological responses [1, 5]. The precise pattern of responses that can be observed does not only depend on the nature of the activated G proteins (receptor subtypes) but also on which specific components of different signaling cascades (e.g. effector enzymes or ion channels) are actually expressed in the studied cell type or tissue. The observed effects can be caused by direct interactions of the activated G protein(s) with effector enzymes or ion channels or may be mediated by second messengers (Ca2+, DP3, etc.) generated upon mAChR stimulation. 

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... 

PARs are coupled to multiple G-proteins and mediate a number of well-defined cellular responses via classical second messenger and kinase pathways. PARs are differentially expressed in cells of the vasculature as well in the brain, lung, gastrointestinal tract, skin as well as other highly vascularised tissues and evidence suggests distinct physiological functions and roles in disease states [2]. 

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