Epinephrine, release

Compared to a,-receptors, a2-receptors have only moderate distribution on the effector tissues however, they have important presynaptic effects. Alpha-one receptors are found on effector tissue cells at the neuroeffector junction the a2-receptors are found on the varicosities of the postganglionic neuron. Norepinephrine released from this neuron not only binds to the a.j-receptors on the effector tissue to cause some physiological effect but also binds to the a2-receptors on the neuron. Alpha-two receptor stimulation results in presynaptic inhibition" or in a decrease in the release of norepinephrine. In this way, norepinephrine inhibits its own release from the sympathetic postganglionic neuron and controls its own activity. Both ar and a2-receptors have equal affinity for norepinephrine released directly from sympathetic neurons as well as circulating epinephrine released from the adrenal medulla. 

Proprioceptors originating in muscles and joints of the exercising limbs provide substantial input to the medullary respiratory center. In fact, even passive movement of the limbs causes an increase in ventilation. Therefore, the mechanical aspects of exercise also contribute to the ventilatory response. The increased metabolism associated with exercise increases body temperature, which further contributes to the increase in ventilation during exercise. (Not surprisingly, ventilation is also enhanced in response to a fever.) Exercise is associated with a mass sympathetic discharge. As a result, epinephrine release from the adrenal medulla is markedly increased. Epinephrine is believed to stimulate ventilation. 

Sympathetic nerves. The afferent and efferent arterioles are densely innervated with sympathetic nerves. Norepinephrine released directly from the nerves or circulating epinephrine released from the adrenal medulla stimulates a, adrenergic receptors to cause vasoconstriction. The predominant site of regulation is the afferent arteriole. Under normal resting conditions, there is little sympathetic tone to these vessels so that RBF is comparatively high. As discussed previously, this facilitates glomerular filtration. 

In contrast, much is known about the catabolism of catecholamines. Adrenaline (epinephrine) released into the plasma to act as a classical hormone and noradrenaline (norepinephrine) from the parasympathetic nerves are substrates for two important enzymes monoamine oxidase (MAO) found in the mitochondria of sympathetic neurones and the more widely distributed catechol-O-methyl transferase (COMT). Noradrenaline (norepinephrine) undergoes re-uptake from the synaptic cleft by high-affrnity transporters and once within the neurone may be stored within vesicles for reuse or subjected to oxidative decarboxylation by MAO. Dopamine and serotonin are also substrates for MAO and are therefore catabolized in a similar fashion to adrenaline (epinephrine) and noradrenaline (norepinephrine), the final products being homo-vanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) respectively. 

Adverse effects. Cardiovascular crises are a possible risk emotional stress of the patient may cause sympathoadrenal activation with epinephrine release. The resulting rise in blood pressure can be all the more marked because persistent depression of sympathetic nerve activity induces supersen-sitivily of effector organs to circulating catecholamines. 

Adrenaline (epinephrine) release from adrenal medulla Stimulation of cutaneous nerve endings, pain and itching H2Controls gastric acid secretion... 

The rise in systolic blood pressure that occurs after epinephrine release or administration is caused by its positive inotropic and chronotropic actions on the heart (predominantly Bj receptors) and the vasoconstriction induced in many vascular beds (a receptors). Epinephrine also activates B2 receptors in some vessels (eg, skeletal muscle blood vessels), leading to their dilation. Consequently, total peripheral resistance may actually fall, explaining the fall in diastolic pressure that is sometimes seen with epinephrine injection (Figure... 

In the absence of food, plasma levels of glucose, amino acids, and triacylglycerols fall, triggering a decline in insulin secretion and an increase in glucagon and epinephrine release. The decreased insulin to glucagon ratio, and the decreased availability of circulating substrates, make the period of nutrient deprivation a catabolic period. 

Autonomic nervous system (A, middle). In analogy to autonomic ganglia, NAChR are found also on epinephrine-releasing cells of the adrenal medulla, which are innervated by spinal first neurons. At all these synapses, the receptor is located postsynaptically in the somatodendritic region of the gangliocyte. 

Kawada, T., Yamazaki, T., Akiyama, T., Sato, T., Shishido, T., Inagaki, M., Tatewaki, T., Yanagiya, Y., Sugimachi, M., Sunagawa, K. (2000). Cyanide intoxication induced exocytotic epinephrine release in rabbit myocardium. J. Auton. Nerv. Syst. 80 137-41. 

With few exceptions, platelets of all species have similar ultrastmctural features and contain similar metabolic pathways. Therefore, species-dependent differences in platelet function tend to be quantitative rather than quantitative. Platelets from larger ruminants, including cattle, sheep, and goats, do not contain an open canalicular system and appear to be less functional than platelets from other species. Platelet function may be less irrqrortant to these species because they are not frequently exposed to trauma in the wild. Alternatively, carnivores are regularly exposed to trauma in the process of hunting and defending themselves. These species tend to have highly functional platelets and also can enhance platelet function at times of excitement or fear as a result of epinephrine release. 

Cryer PE, Haymond MW, Santiago JV, et al. Norepinephrine and epinephrine release and adrenergic mediation of smoking-associated hemodynamic and metabolic events. NEJM 1976 295 573-7. 

The neuronal monoamme transporters provide the principal mechanism for rapid termmation of the signal in neuronal transmission, whereas the transporters at extraneuronal locations are more important for limiting the spread of the signal and for clearance of catecholamines from the bloodstream. For the norepinephrine released by sympathetic nerves, about 90% is removed back into nerves by neuronal uptake, 5% is removed by extraneuronal uptake, and 5% escapes these processes to enter the bloodstream. In contrast, for the epinephrine released directly into the bloodstream from the adrenals, about 90% is removed by extraneuronal monoamine transport processes that are particularly important in the liver. The presence of these highly active transport processes means that monoamines are rapidly cleared from the bloodstream with a circulatory half-life of less than 2 minutes. 

Human deaths following 1,1,1 -trichloroethane inhalation are often attributed to cardiac arrhythmias (Guberan et al. 1976 MacDougall et al. 1987 Travers 1974). Such conclusions are based on animal studies in which arrhythmias have been produced during or immediately following acute inhalation exposure to 1,1,1 -trichloroethane (Carlson 1981 Clark and Tinston 1973 Reinhardt et al. 1973 Trochimowicz et al. 1974). The mechanism for the arrhythmias apparently involves sensitization of the heart to endogenous epinephrine. The exposure level at which cardiac sensitization occurs in humans is not known, but in animals, concentrations as low as 5,000 ppm are effective after only 10 minutes of inhalation (Reinhardt et al. 1973). Physical exertion, stress, or any other stimulus of epinephrine release from the adrenal medulla may render an individual more vulnerable to 1,1,1-trichloroethane. Hypoxia may further increase a subject s susceptibility. 

The catecholamines epinephrine, norepinephrine, and dopamine are inactivated by oxidation reactions catalyzed by monoamine oxidase (MAO) (Figure 15.10). Because MAO is found within nerve endings, catecholamines must be transported out of the synaptic cleft before inactivation. (The process by which neurotransmitters are transported back into nerve cells so that they can be reused or degraded is referred to as reuptake.) Epinephrine, released as a hormone from the adrenal gland, is carried in the blood and is catabolized in nonneural tissue (perhaps the kidney). Catecholamines are also inactivated in methylation reactions catalyzed by catechol-O-methyltransferase (COMT). These two enzymes (MAO and COMT) work together to produce a large variety of oxidized and methylated metabolites of the catecholamines. 

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