Epinephrine storage

The sympathetic or adrenergic nervous system operates in juxtaposition to the parasympathetic nervous system to maintain homeostasis in response to physical activity and physical or psychological stress. Sympathomimetic neurotransmission is generally mediated by norepinephrine [51-41 -2] (1), CgH NO, released from presynaptic storage granules upon stimulation. A second endogenous sympathomimetic agent, epinephrine [51-43-4] (2),... 

Storage and utilization of tissue glycogen, maintenance of blood glucose concentration, and other aspects of carbohydrate metabolism are meticulously regulated by hormones, including insulin, glucagon, epinephrine, and the glucocorticoids. 

It has been found that epinephrine solutions having a physiological pH and which are stable for months in storage can be prepared by combining with the epinephrine a small amount of sodium bisulfite, boric acid, and oxine (8-hydroxy-quinoline) hereinafter called 8-quinoli-nol and adjusting the pH with an alkali, such as sodium hydroxide, to the desired pH. 

Ordinarily, low concentrations of catecholamines are free in the cytosol, where they may be metabolized by enzymes including monoamine oxidase (MAO). Thus, conversion of tyrosine to l-DOPA and l-DOPA to dopamine occurs in the cytosol dopamine then is taken up into the storage vesicles. In norepinephrine-containing neurons, the final P-hydroxylation occurs within the vesicles. In the adrenal gland, norepinephrine is N-methylated by PNMT in the cytoplasm. Epinephrine is then transported back into chromaffin granules for storage. 

Biosynthesis and degradation of glycosaminoglycans biosynthesis of collagen, mineralization and demineralization of bone. Fatty acid synthesis and triglyceride storage in adipocytes promoted by insulin and triglyceride hydrolysis and fatty acid release stimulated by glucagon and adrenaline (epinephrine). 

Several of the neurotransmitters are small-molecule amines such as dopamine, serotonin, epinephrine, and norepinephrine. These neurotransmitters are synthesized in the cytoplasm of the axon terminal and subsequently transported into and stored within the synaptic vesicles. The amino acids glycine and glutamic acid are normal constituents of proteins and are present in abundance in the axons. These are also stored in synaptic vesicles. Each electrical impulse that arrives at the presynaptic side of a synapse will cause only a small minority of the synaptic vesicles to fuse with the plasma membrane and discharge their contents. The remaining synaptic vesicles remain, waiting for subsequent electrical impulses. At the same time, neurotransmitter synthesis continues, as does their storage in synaptic vesicles. This tends to restore the full complement of amine neurotransmitters at the axon terminal. 

Cuanethidine possesses high affinity for the axolemmal and vesicular amine transporters, it is stored instead of NE, but is unable to mimic the functions of the latter, in addition, it stabilizes the axonal membrane, thereby impeding the propagation of impulses into the sympathetic nerve terminals. Storage and release of epinephrine from the adrenal medulla are not affected, owing to the absence of a re-uptake process. The drug does not cross the blood-brain barrier. 

Pharmacology These drugs are non-selective MAOIs and cause an increase in the concentration of endogenous epinephrine, norepinephrine, and serotonin (5HT) in storage sites throughout the nervous system. 

MecfianismofAction An antidepressant that inhibits the MAO enzyme system at central nervous system (CNS) storage sites. The reduced MAO activity causes an increased concentration in epinephrine, norepinephrine, serotonin, and dopamine at neuron receptor sites. Therapeutic Effect Produces antidepressant effect. 

Mechanism of Action An MAOI that inhibits the activity of the enzyme monoamine oxidase at CNS storage sites, leading to increased levels of the neurotransmitters epinephrine, norepinephrine, serotonin, and dopamine at neuronal receptor sites. Therapeutic Effect Relieves depression. 

NE molecules are made inside into synaptic vesicles by the vesicular monoamine transporter (VMAT). This transport is an active, adenosine triphosphate (ATP)-requiring process. VMAT also transports DA, epinephrine and serotonin (5-HT). These hormones and transmitters are so-called monoamines (MO). Certain drugs, such as reserpine and tetrabenazine, inhibit the VMAT and suppress vesicular MO storage (Reinhard et al., 1988 Russo et al., 1994). 

Storage of norepinephrine in vesicles Dopamine is transported into synaptic vesicles by an amine transporter system that is also involved in the re-uptake of preformed norepinephrine. This carrier system is blocked by reserpine (see p. 78). Dopamine is hydroxylated to form norepinephrine by the enzyme, dopamine 3-hydroxylase. Synaptic vesicles contain dopamine or norepinephrine plus adenosine triphosphate and the 3-hydroxylase. Not all of the norepinephrine is packaged in vesicles some exists in a cytoplasmic pool that can be displaced. In the adrenal medulla, norepinephrine is methylated to yield epinephrine both are stored in chromaffin cells. On stimulation, the adrenal medulla releases about 85% epinephrine and 15% norepinephrine. 

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