Messengers cyclic-AMP

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. 

When epinephrine binds to cells, it stays outside on the membrane-bound receptor. The second messenger, cyclic AMP, is made by the enzyme adenylate cyclase. 

Fig. 1. A model for the pleiotropic effects of LH on functions of Leydig cells. LH interacts with its specific receptor in the plasma membrane of the Leydig cell which results in the activation of several transducing systems and the formation of several second messengers (cyclic AMP, Ca2+, diacylglycerol and arachidonic acid metabolites). Protein kinases (A, C and calmodulin dependent) are activated resulting in the phosphorylation of specific proteins and the synthesis of specific proteins. The (phospho)proteins are involved in the transport of cholesterol to, and the control of, cholesterol metabolism in the inner mitochondrial membrane. Arachidonic acid metabolites (prostaglandins, leukotrienes) may also control steroidogenesis. LH can also regulate the secretion of proteins. The trophic effects of LH are manifested in the growth and differentiation of the Leydig cells.

ACTH stimulates the synthesis of steroids by the cells of the adrenal cortex. The steroidogenic action of ACTH is mediated primarily by the intracellular messenger cyclic AMP acting via cyclic AMP-dependent protein kinase. The evidence for this is that (i) ACTH stimulates cyclic AMP production in intact adrenocortical cells and in plasma membrane preparations (ii) cyclic AMP analogues added to adrenocortical cells stimulate steroidogenesis to the same extent as ACTH and (iii) mutant adrenocortical cells with defective cyclic AMP-dependent protein kinase lack stimulation of steroidogenesis by ACTH [2],... 

The GTP-bound form of the a subunit of Gj. activates adenylate cyclase, a transmembrane protein that catalyzes the formation of the secondary messenger cyclic AMP from ATP. 

The message is now carried by the alphas subunit which interacts with a membrane-bound enzyme called adenylate cyclase and switches it on. This enzyme then catalyses the synthesis of the secondary messenger—cyclic AMP—which moves into the cell s cytoplasm and proceeds to activate enzymes called protein kinases. 

Following G-protein activation comes initiation of effector mechanisms. For example, this can include activation of the enzyme adenylyl cyclase to produce the second messenger cyclic AMP. This and other second messengers go on to activate enzymatic biochemical cascades within the cell. A second layer of response observation is the measurement of the quantity of these second messengers. Yet another layer of response is the observation of the effects of the second messengers. Thus, activation of enzymes such as MAP kinase can be used to monitor dmg activity. 

The CBl and CBj cannabinoid receptors in nervous, immune, and other tissues of the body participate in G protein-mediated signal transduction pathways. Particularly well characterized are those that regulate the second messengers cyclic AMP, Ca ", and perhaps IP3. CBi receptors are modulators of ion channels, which makes them key players in the control of neurotransmission. These receptors also partic-... 

There are two major types of vasopressin receptors, VI and V2. The VI receptor occurs in vascular smooth muscle and is coupled via to activation of the phosphoinositide cascade-signaling system and generation of the second messenger inositol trisphosphate (IP3) and diacylglycerol. V2 receptors are found in kidney and are coupled via to activation of adenylate cyclase and production of the second messenger cyclic AMP. 

Hormones act through binding to specific cellular receptors. Second messengers are often used to transmit the hormonal message to the target metabolic pathway. cAMP is one such second messenger. Cyclic AMP -dependent signal transduction mechanisms involve three separate proteins (1) a hormone receptor, (2) adenylate cyclase, and (3) a G protein (see here). 

Beta-adrenergic agonists bind to receptors on bronchial smooth muscle, causing an increase in the biochemical messenger, cyclic AMP (cAMP). Increased levels of cAMP cause relaxation of bronchial muscle cells, resulting in bronchodilation. 

Two of the most important second messengers, cyclic AMP (cAMP) and phosphatidylinositol-4,5- ii5phosphate (PlPg), activate protein kinases, which phosphorylate key enzymes. Calcium ion is intimately involved in the action of PlPg. 

Phosphorylase, which catalyses glycogen breakdown, provides an example of covalent modification in response to the concentration of the second messenger , cyclic AMP (see Hormones). Phosphorylase in its inactive (b) form is activated by phosphorylation of a serine residue. In muscle phosphorylase, this causes the dimeric b form of the enzyme to aggregate to a tetramer, the active a form (in liver,... 

Long chain fatty acids derived from the adipose tissue are released through the action of the adipose tissue lipase (Vaughan et al., 1964) and the free fatty acids released from the adipose tissue are transported in the circulation bound to albumin. As it well known, lipase activity increases in response to p-adrenergic stimulation via the activation of adenyl cyclase and the second messenger, cyclic AMP (Butcher, 1972). On the other hand,... 

---