Second messengers table

The GABAB-receptors, the muscarinic M2- and IVU-receptors for acetylcholine, the dopamine D2-, D3-and D4-receptors, the a2-adrenoceptors for noradrenaline, the 5-HTiA F-receptors for serotonin, and the opioid p-, 8- and K-receptors couple to G proteins of the Gi/o family and thereby lower [1] the cytoplasmic level of the second messenger cyclic AMP and [2] the open probability ofN- andP/Q-type Ca2+ channels (Table 1). The muscarinic Mr, M3- and M5-receptors for acetylcholine and the ai-adrenoceptors for noradrenaline couple to G proteins of the Gq/11 family and thereby increase the cytoplasmic levels of the second messengers inositol trisphosphate and diacylglycerol (Table 1). The dopamine Dr and D5-receptors and the (3-adrenoceptors for noradrenaline, finally, couple to Gs and thereby increase the cytoplasmic level of cyclic AMP. 

The mitogen-activated protein kinase cascade is second-messenger-independent. Although the second-messenger-dependent protein kinases were identified first as playing an important role in neuronal function, we now know that many other types of protein serine-threonine kinase are also essential (Table 23-1). Indeed, one of the most critical discoveries of the 1990s was the delineation of the mitogen-activated protein kinase (MAP kinase or MAPK) cascades. 

The brain contains many other types of second-messenger-independent protein kinases. Examples of other second-messenger-independent protein kinases are listed in Table 23-1. Many of these include enzymes that were identified originally in association with a particular substrate protein but shown later to play a more widespread role in brain signal transduction. The functional role of one of these, [3-adrenergic receptor kinase (PARK), a type of G protein receptor kinase (GRK), is discussed further below. 

There are many examples of phosphorylation/dephosphorylation control of enzymes found in carbohydrate, fat and amino acid metabolism and most are ultimately under the control of a hormone induced second messenger usually, cytosolic cyclic AMP (cAMP). PDH is one of the relatively few mitochondrial enzymes to show covalent modification control, but PDH kinase and PDH phosphatase are controlled primarily by allosteric effects of NADH, acetyl-CoA and calcium ions rather than cAMP (see Table 6.6). 

A protein kinase is an enzyme that phosphorylates many other proteins, changing their activity (e.g., phosphorylation of acetyl CoA carboxylase inhibits it). Examples of protein kinases ate listed in Table 1-9-2 along with the second messengers that activate them. 

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 ). 

A selection of other tumor suppressor genes is summarized in Table 14.2. Interestingly, an enzyme of phosphatidyl-inositol metabolism has been also identified as a tumor suppressor. The PTEN tumor suppressor gene codes for a phospholipid phosphatase which specifically cleaves a phosphate from the second messenger phosphatidyl-inosi-tol-3,4,5-trisphosphate (PtdInsPj, see 6.6.2). and thus inactivates the messenger (review Maehama and Dixon, 1999). ... 

Table 1.1 G protein-coupled receptors, their effector systems, and intracellular second messengers...

As indicated in Chapter 6, muscarinic receptor subtypes have been characterized by binding studies and cloned. Several cellular events occur when muscarinic receptors are activated, one or more of which might serve as second messengers for muscarinic activation. All muscarinic receptors appear to be of the G protein-coupled type (see Chapter 2 and Table 7-1). Muscarinic agonist binding activates the inositol trisphosphate (IP3), diacylglycerol (DAG) cascade. Some evidence... 

TABLE 12-4 Some Signals That Use cAMP as Second Messenger... 

Catecholamines produced in the brain and in other neural tissues function as neurotransmitters, but epinephrine and norepinephrine are also hormones, synthesized and secreted by the adrenal glands. Like the peptide hormones, catecholamines are highly concentrated within secretory vesicles and released by exocytosis, and they act through surface receptors to generate intracellular second messengers. They mediate a wide variety of physiological responses to acute stress (see Table 23-6). 

The known regulatory effects of insulin (Table 17-3) often involve phosphorylation of serine or threonine side chains on specific proteins. The tyrosine kinase of the activated insulin receptors does not catalyze such phosphorylation. Therefore, it seems likely that one or more second messengers or mediator substances are needed. Much effort has gone into searching for... 

Table 2-1. A Partial List of Endogenous Ligands and Their Associated Second Messengers. ...

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