Adrenaline glycogenolysis stimulation

Figure 12.5 Effector mechanism activation of a membrane-bound phospholipase. An example is activation of a membrane-bound phospholipase which hydrolyses phosphatidylinositol bisphosphate (PIP2) and results in the formation of the two messengers, inositol trisphosphate (IP3) and diacylglycerol (DAG). Messenger IP3 binds to a receptor on the endoplasmic reticulum that results in release of Ca ions into the cytosol. DAG, which remains within the membrane, activates protein kinase-C at the membrane surface. When the kinase leaves the membrane, it is unclear how it remains active or loss of activity is prevented, so that it can phosphorylate proteins in the cytosol or even the nucleus. An example is adrenaline binding to the a-receptor in the liver, in which Ca ions stimulate glycogenolysis.

Activation of Gs or Gi proteins results in stimulation or inhibition, respectively, of adenylyl cyclase which catalyses the formation of cyclic adenosine monophosphate (cAMP) from ATP The cAMP binds to protein kinase A (PKA), which mediates the diverse cellular effects of cAMP by phosphorylating substrate enzymes, thereby increasing their activity. Among the responses mediated by cAMP are increases in contraction of cardiac and skeletal muscle and glycogenolysis in the liver by adrenaline (epinephrine). Because a single activated receptor can cause the conversion of up to 100 inactive Gs proteins to the active form, and each of these results in the synthesis of several hundred cAMP molecules, there is a very considerable signal amplification. For example, adrenaline concentrations as low as 10-10 M can stimulate the release of glucose sufficient to increase... 

The existence of two different adrenergic receptors was first suggested by Ahlquist (1948) Those responses evoked most readily by noradrenaline (norepinephrine), less by adrenaline 7.43), still less by isoprenaline 12.44) and least by A -/-butylnorepinephrine are credited to a-receptors those for which this sequence runs in the reverse direction are credited to jS-receptors. Typical a-responses are constriction of blood-vessels, stimulation of the uterus, relaxation of the intestine. Typical jS-responses are dilatation of blood-vessels, relaxation of the uterus, stimulation of muscle glycogenolysis, production of tachycardia (Levy and Ahlquist, 1961). 

The actions of adrenalin, [8-arginine]vasopressin, and angiotensin have confirmed that the degradation of liver glycogen is stimulated by a wide variety of hormones. The effects of hormones on the turnover of glycogen in perfused rat liver has been examined, particularly the control of glycogenolysis by hormones that may or may not be cAMP-dependent. Chlorothiazide inhibited the accumulation and utilization of glycogen by slices of canine aorta in vitro. ° ... 

There are two types of cell membrane receptor (a and jS) for adrenaline. -Receptors which are inhibited by -blockers such as propanolol are the main type of receptor in muscle, heart, adipose tissue and many other tissues. They interact with and activate adenylate cyclase in the cell membrane so that the effect of adrenaline on muscle or adipose tissue is to increase the concentration of cAMP in the cell and thus to activate protein kinase. Stimulation of glycogen breakdown by adrenaline in muscle is then mediated by a cascade mechanism similar to that involved in the stimulation of glycogenolysis in liver by glucagon (page 353). Breakdown of triglycerides in adipose tissue, as in liver, occurs as a result of activation of triglyceride lipase by phosphorylation. 

A hormone secreted by the adrenal medulla. It stimulates the sympathetic nervous system causing bronchodilatation, vasoconstriction and increased heart rate, which together raise the blood pressure. Adrenaline also increases glycogenolysis and lipolysis and this can increase blood levels of glucose and fatty acids. 

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