Dopamine and norepinephrine are embracing their immune side and so should we.

While the history of neuroimmunology is long, the explicit study of neuroimmune communication, and particularly the role of catecholamines in neuroimmunity, is still emerging. Recent studies have shown that catecholamines, norepinephrine, epinephrine, and dopamine, are central to multiple complex mechanisms regulating immune function. These studies show that catecholamines can be released from both the nervous system and directly from immune cells, mediating both autocrine and paracrine signaling. This commentary highlights the importance of catecholaminergic immunomodulation and discusses new considerations needed to study the role of catecholamines in immune homeostasis to best leverage their contribution to disease processes for the development of new therapeutic approaches.

The separate and combined effects of a dangerous context and an epinephrine injection on sensory preconditioning in rats.

Four experiments examined the effects of a dangerous context and a systemic epinephrine injection on sensory preconditioning in rats. In each experiment, rats were exposed to presentations of a tone and light in stage 1, light-shock pairings in stage 2, and test presentations of the tone alone and light alone in stage 3. Presentations of the tone and light in stage 1 occurred in either a safe or a previously shocked context, and/or under a systemic injection of epinephrine. Experiment 1 showed that a trace interval of 20 sec between presentations of the tone and light produced sensory preconditioning of the tone in a previously shocked context but not in a safe context, while experiment 2 provided evidence that this trace preconditioning was associative, due to the formation of a tone-light association. Experiment 3 showed that, in a safe context, exposure to the trace protocol under the influence of an epinephrine injection also produced sensory preconditioning of the tone, while experiment 4 provided evidence that a shocked context and an epinephrine injection have additive effects on trace preconditioning. These findings are discussed in relation to theories of trace conditioning. They suggest that the release of epinephrine by danger enhances attention and/or working memory processes, and thereby associative formation across a trace interval.

Hypothalamic MC4R regulates glucose homeostasis through adrenaline-mediated control of glucose reabsorption via renal GLUT2 in mice.

AIMS/HYPOTHESIS: Melanocortin 4 receptor (MC4R) mutation is the most common cause of known monogenic obesity in humans. Unexpectedly, humans and rodents with MC4R deficiency do not develop hyperglycaemia despite chronic obesity and insulin resistance. To explain the underlying mechanisms for this phenotype, we determined the role of MC4R in glucose homeostasis in the presence and absence of obesity in mice. METHODS: We used global and hypothalamus-specific MC4R-deficient mice to investigate the brain regions that contribute to glucose homeostasis via MC4R. We performed oral, intraperitoneal and intravenous glucose tolerance tests in MC4R-deficient mice that were either obese or weight-matched to their littermate controls to define the role of MC4R in glucose regulation independently of changes in body weight. To identify the integrative pathways through which MC4R regulates glucose homeostasis, we measured renal and adrenal sympathetic nerve activity. We also evaluated glucose homeostasis in adrenaline (epinephrine)-deficient mice to investigate the role of adrenaline in mediating the effects of MC4R in glucose homeostasis. We employed a graded [13C6]glucose infusion procedure to quantify renal glucose reabsorption in MC4R-deficient mice. Finally, we measured the levels of renal glucose transporters in hypothalamus-specific MC4R-deficient mice and adrenaline-deficient mice using western blotting to ascertain the molecular mechanisms underlying MC4R control of glucose homeostasis. RESULTS: We found that obese and weight-matched MC4R-deficient mice exhibited improved glucose tolerance due to elevated glucosuria, not enhanced beta cell function. Moreover, MC4R deficiency selectively in the paraventricular nucleus of the hypothalamus (PVH) is responsible for reducing the renal threshold for glucose as measured by graded [13C6]glucose infusion technique. The MC4R deficiency suppressed renal sympathetic nerve activity by 50% in addition to decreasing circulating adrenaline and renal GLUT2 levels in mice, which contributed to the elevated glucosuria. We further report that adrenaline-deficient mice recapitulated the increased excretion of glucose in urine observed in the MC4R-deficient mice. Restoration of circulating adrenaline in both the MC4R- and adrenaline-deficient mice reversed their phenotype of improved glucose tolerance and elevated glucosuria, demonstrating the role of adrenaline in mediating the effects of MC4R on glucose reabsorption. CONCLUSIONS/INTERPRETATION: These findings define a previously unrecognised function of hypothalamic MC4R in glucose reabsorption mediated by adrenaline and renal GLUT2. Taken together, our findings indicate that elevated glucosuria due to low sympathetic tone explains why MC4R deficiency does not cause hyperglycaemia despite inducing obesity and insulin resistance. Graphical abstract.

GATA2 functions in adrenal chromaffin cells.

Catecholamine synthesized in the sympathoadrenal system, including sympathetic neurons and adrenal chromaffin cells, is vital for cardiovascular homeostasis. It has been reported that GATA2, a zinc finger transcription factor, is expressed in murine sympathoadrenal progenitor cells. However, a physiological role for GATA2 in adrenal chromaffin cells has not been established. In this study, we demonstrate that GATA2 is specifically expressed in adrenal chromaffin cells. We examined the consequences of Gata2 loss-of-function mutations, exploiting a Gata2 conditional knockout allele crossed to neural crest-specific Wnt1-Cre transgenic mice (Gata2 NC-CKO). The vast majority of Gata2 NC-CKO embryos died by embryonic day 14.5 (e14.5) and exhibited a decrease in catecholamine-producing adrenal chromaffin cells, implying that a potential catecholamine defect might lead to the observed embryonic lethality. When intercrossed pregnant dams were fed with synthetic adrenaline analogs, the lethality of the Gata2 NC-CKO embryos was partially rescued, indicating that placental transfer of the adrenaline analogs complements the lethal catecholamine deficiency in the Gata2 NC-CKO embryos. These results demonstrate that GATA2 participates in the development of neuroendocrine adrenaline biosynthesis, which is essential for fetal survival.

Suppression of the innate cancer-killing activity in human granulocytes by stress reaction as a possible mechanism for affecting cancer development.

Psychological stress may be linked to cancer incidence; however, more direct evidence is required to support this viewpoint. In this study, we investigated the effects of stress on immunosurveillance against cancer cells using a previously established examination stress model. We showed that the cancer killing activity (CKA) of granulocytes (also known as polymorphic nuclear cells, PMNs) is sharply reduced during examination stress stimulation in some donors who are psychologically sensitive to examination stress, with the concentration of plasma stress hormones (cortisone, epinephrine, and norepinephrine) increasing accordingly. The effects of stress hormones on immune cell CKA were also investigated under two in vitro co-incubation conditions, with all three hormones found to exert inhibitory effects on the CKA of PMNs and mononuclear cells. We showed that stress triggered the release of stress hormones which had profound inhibitory effects on the innate anticancer functions of PMNs. These results provide a possible explanation for the relationship between psychological stress and cancer incidence.

Diverse Effects of Noradrenaline and Adrenaline on the Quantal Secretion of Acetylcholine at the Mouse Neuromuscular Junction.

Despite the long history of investigations of adrenergic compounds and their biological effects, specific mechanisms of their action in distinct compartments of the motor unit remain obscure. Recent results have suggested that not only skeletal muscles but also the neuromuscular junctions represent important targets for the action of catecholamines. In this paper, we describe the effects of adrenaline and noradrenaline on the frequency of miniature endplate potentials, the quantal content of the evoked endplate potentials and the kinetics of acetylcholine quantal release in the motor nerve endings of the mouse diaphragm. Noradrenaline and adrenaline decreased the frequency of the spontaneous release of acetylcholine quanta. The effect of noradrenaline was prevented by the ß adrenoreceptor blocker propranolol, whereas the action of adrenaline was abolished by the α adrenoreceptor antagonist phentolamine. Noradrenaline did not alter the quantal content of endplate potentials, while adrenaline suppressed the evoked release of acetylcholine. Blocking the α adrenoreceptors prevented the decrease in quantal secretion caused by adrenaline. Quantal release became more asynchronous under noradrenaline, as evidenced by a greater dispersion of real synaptic delays; in contrast, adrenaline synchronized the release process. Our data suggest an involvement of α and ß adrenoreceptors in the diverse modulation of the frequency of miniature endplate potentials, the quantal content of the evoked endplate potentials and the kinetics of acetylcholine quantal secretion in the mouse neuromuscular junction. Moreover, the adrenoblockers affected both the evoked and spontaneous quantal release of acetylcholine, suggesting the presence of endogenous catecholamines in the vicinity of cholinergic synapses.

Regulation of Hepatic Follistatin Expression at Rest and during Exercise in Mice.

INTRODUCTION: Follistatin (FST) is a protein with numerous biological roles and was recently identified as an exercise-inducible hepatokine; however, the signals that regulate this are not well understood. The purpose of this study was to delineate potential endocrine factors that may regulate hepatic FST at rest and during exercise. METHODS: This study used four experiments. First, male and female C57BL/6J mice remained sedentary or were subjected to a single bout of exercise at moderate or exhaustive intensity with liver collected immediately post. Second, mice were injected with glucagon (1 mg·kg, 60 min), epinephrine (2 mg·kg, 30 min), glucagon then epinephrine, or saline. Third, mice were pretreated with propranolol (20-60 mg·kg, 30 min) before epinephrine injection. Fourth, glucagon receptor wild type (Gcgr) or knockout (Gcgr) mice were pretreated with saline or propranolol (20 mg·kg, 30 min) and were subjected to a single bout of exhaustive exercise with liver collected immediately post or after 2 h recovery. In all experiments liver FST mRNA expression was measured, and in experiment four FST protein content was measured. RESULTS: A single bout of treadmill exercise performed at an exhaustive but not moderate-intensity increased FST expression, as did injection of glucagon or epinephrine alone and when combined. Pretreatment of mice with propranolol attenuated the epinephrine-induced increase in FST expression. The exercise-induced increase in FST expression was attenuated in Gcgr mice, with no effect of propranolol. Gcgr mice had higher protein content of FST, but there was no effect of exercise or propranolol. CONCLUSIONS: These data suggest that both glucagon and epinephrine regulate hepatic FST expression at rest; however, only glucagon is required for the exercise-induced increase.

A long-term perspective on cardiovascular job stress research.

This review provides perspectives on cardiovascular occupational stress research since the 1960s until now. The author argues for closer links between basic science and clinical follow-up examinations of patients. In an excellent way urinary excretion of adrenaline and noradrenaline during wake hours mirrors day to day or week to week variations in sympathomedullary activity which could be related to variations in the patient's and cardiovascular and psychosocial situation. Modern methods for following variations over time in heart contractility should also be related to the patients' psychosocial situation. In addition the author argues for more extensive use of the increasing knowledge regarding regeneration and vagal activity in relation to variations in job conditions and development or prevention of cardiovascular disease.

Adrenaline activation of the carotid body: Key to CO2 and pH homeostasis in hypoglycaemia and potential pathological implications in cardiovascular disease.

Ventilatory and neuroendocrine counter-regulatory responses during hypoglycaemia are essential in order to maintain glycolysis and prevent rises in PaCO2 leading to systemic acidosis. The mammalian carotid body has emerged as an important driver of hyperpnoea and glucoregulation in hypoglycaemia. However, the adequate stimulus for CB stimulation in hypoglycaemia has remained controversial for over a decade. The recent finding that adrenaline is a physiological activator of CB in hypoglycaemia raises the intriguing possibility that CB stimulation and hyperpnoea may be necessary to maintain pH in other adrenaline-related hypermetabolic states such as exercise. This review will therefore focus on 1) The important functional contribution of the CB in the counter-regulatory and ventilatory response to hypoglycaemia, 2) the proposed mechanisms that cause CB stimulation in hypoglycaemia including hormonal activation by adrenaline and direct low glucose sensing and 3) the possible pathological consequences of repetitive CB activation by adrenaline that could potentially be targeted to reduce CB-mediated cardiovascular disease.

Circulating epinephrine is not required for chronic stress to enhance metastasis.

Signaling through ß-adrenergic receptors drives cancer progression and ß-blockers are being evaluated as a novel therapeutic strategy to prevent metastasis. Orthotopic mouse models of breast cancer show that ß-adrenergic signaling induced by chronic stress accelerates metastasis, and that ß2-adrenergic receptors on tumor cells are critical for this. Endogenous catecholamines are released during chronic stress: norepinephrine from the adrenal medulla and sympathetic nerves, and epinephrine from the adrenal medulla. ß2-adrenergic receptors are much more sensitive to epinephrine than to norepinephrine. To determine if epinephrine is necessary in the effects of stress on cancer progression, we used a denervation strategy to eliminate circulating epinephrine, and quantified the effect on metastasis. Using both human xenograft and immune-intact murine models of breast cancer, we show that circulating epinephrine is dispensable for the effects of chronic stress on cancer progression. Measured levels of circulating norepinephrine were sufficiently low that they were unlikely to influence ß2-adrenergic signaling, suggesting a possible role for norepinephrine release from sympathetic nerve terminals.

Adrenergic and adenosinergic regulation of the cardiovascular system in an Antarctic icefish: Insight into central and peripheral determinants of cardiac output.

Icefishes characteristically lack the oxygen-binding protein haemoglobin and therefore are especially reliant on cardiovascular regulation to augment oxygen transport when oxygen demand increases, such as during activity and warming. Using both in vivo and in vitro experiments, we evaluated the roles for adrenaline and adenosine, two well-established cardio- and vasoactive molecules, in regulating the cardiovascular system of the blackfin icefish, Chaenocephalus aceratus. Despite increasing cardiac contractility (increasing twitch force and contraction kinetics in isometric myocardial strip preparations) and accelerating heart rate (ƒH), adrenaline (5 nmol kg-1 bolus intra-arterial injection) did not significantly increase cardiac output (Q̇) in vivo because it elicited a large decrease in vascular conductance (Gsys). In contrast, and despite preliminary data suggesting a direct negative inotropic effect of adenosine on isolated atria and little effect on isolated ventricle strips, adenosine (500 nmol kg-1) generated a large increase in Q̇ by increasing Gsys, a change reminiscent of that previously reported during both acute warming and invoked activity. Our data thus illustrate how Q̇ in C. aceratus may be much more dependent on peripheral control of vasomotor tone than direct regulation of the heart.

Adrenergic signaling molecular complexes. / Complejos moleculares de la señalización adrenérgica.

Adrenaline and noradrenaline bind to membrane receptors of the superfamily of G protein-coupled receptors (GPCR) in target cells, where they modulate physiological responses such as metabolism, vasoconstriction, vasodilation and proliferation. Alteration in their function is associated with conditions such as hypertension, benign prostatic hyperplasia and cardiac hypertrophy. In response to adrenaline, receptors form signaling complexes, which enables adrenergic action to be specific, rapid and efficient. These signaling complexes or signalosomes are composed of kinases, phosphatases, and adapter and scaffold proteins, which together modulate the receptor function. Manipulation of each protein-protein interaction of the adrenergic signaling complex emerges as a promising therapeutic strategy for the design of drugs that modulate adrenergic action and help to define its pathophysiological significance. An important biological model to perform these investigations is the heart, since it expresses all adrenergic receptors; to date, several heart signalosomes have been described. Mass spectrometry (proteomics), genetic manipulation and biochemical assays, such as two-hybrid and co-immunoprecipitation assays, are tools that are used in these studies.

La adrenalina y la noradrenalina se unen a receptores membranales de la superfamilia de receptores acoplados a proteínas G (GPCR) en las células blanco, donde modulan respuestas fisiológicas tales como el metabolismo, vasoconstricción, vasodilatación y proliferación. La alteración en su función está asociada con hipertensión, hiperplasia prostática benigna e hipertrofia cardiaca. En respuesta a la adrenalina, los receptores forman complejos de señalización, lo que permite que la acción adrenérgica sea específica, rápida y eficiente. Estos complejos de señalización o signalosomas están integrados por cinasas, fosfatasas, proteínas adaptadoras y de andamio, que en conjunto modulan la función del receptor. La manipulación de cada interacción proteína-proteína del complejo de señalización adrenérgico emerge como una estrategia terapéutica prometedora para el diseño de fármacos que modulen la acción adrenérgica y ayuden a definir su significado fisiopatológico. Un modelo biológico importante para realizar estos estudios es el corazón, ya que expresa todos los receptores adrenérgicos; en la actualidad se han descrito varios signalosomas cardiacos. La espectrometría de masas (proteómica), manipulación genética y ensayos bioquímicos como el doble híbrido o la coinmunoprecipitación son herramientas que se emplean en estos estudios.

Epinephrine augments posttetanic potentiation in mouse skeletal muscle with and without myosin phosphorylation.

Sympathetic tone may influence force potentiation, that is, the stimulation-induced increase in skeletal muscle mechanical function associated with myosin phosphorylation, although the mechanism for this effect remains unknown. The purpose of this study was to examine the influence of epinephrine on concentric twitch force potentiation of wild-type and skeletal myosin light-chain kinase devoid mouse muscle (skMLCK-/- ). To this end, concentric twitch force was assessed before and after a potentiating stimulus (PS) to determine the peak and the duration of potentiation in the absence (-EPI) and presence (+EPI) of 1 µmol/L epinephrine in both genotypes. Twitch force of wild-type and skMLCK-/- muscles was increased by up to 31 and 35% and 18 and 23% in the -EPI and EPI conditions, respectively (all data n = 8, P < 0.05). In wild-type muscles, the PS increased RLC phosphorylation from 0.14 ± 0.05 (rest) to 0.66 ± 0.08 mol phos mol RLC; by 480 sec RLC phosphorylation had returned to baseline (all data n = 4 each time point, P < 0.05). Neither resting nor peak levels of RLC phosphorylation were altered by +EPI, although the duration of RLC phosphorylation was prolonged. In skMLCK-/- muscles, RLC phosphorylation was not elevated above constituent levels by stimulation in either the -EPI or +EPI condition. Thus, given the similarity in potentiation responses between genotypes our data suggest that the influence of epinephrine on potentiation was independent of skMLCK catalyzed phosphorylation of the RLC, although the clinical significance of this pathway for skeletal muscle function remains to be identified.

Neurotransmitters in hermatypic coral, Acropora spp., and its contribution to synchronous spawning during reproductive event.

Synchronous spawning as mass reproduction is well known to occur in many hermatypic corals, which is one of the mysterious life birth events. However, its contributing mechanism has not yet been clarified. This study placed focus on elucidating a neurotransmitter as endocrine signals that contribute to the synchronous spawning. First, the determination method of the neurotransmitters in coral was established by LC/MS in the selective ion mode together with a solid phase extraction method. As a result, the similar contents of the neurotransmitters for dopamine (DA), adrenaline (AD) and noradrenaline (NR) were detected in both the hermatypic corals of Acropora intermedia and Acropora digitifera. More interestingly, these neurotransmitters increased through the reproductive event during the synchronous spawning of A. intermedia, particularly, remarkable changes in the NR and DA were observed. In addition, hydrogen peroxide is known as the spawning stimulant and the metabolic by-product of the neurotransmitters, which was exposed to A. digitifera, then the neurotransmitters increased as well as those of the synchronization of spawning. All of the results suggested that the neurotransmitters contribute to the synchronous spawning in the hermatypic corals.

The expression of thioredoxin-1 in acute epinephrine stressed mice.

Stress, a state of perceived threat to homeostasis, regulates a panel of important physiological functions. The human mind and body respond to stress by activating the sympathetic nervous system and secreting the catecholamines epinephrine and norepinephrine in the "fight-or-flight" response. However, the protective mechanism of acute stress is still unknown. In the present study, an acute stress mouse model was constructed by intraperitoneal injection of epinephrine (0.2 mg kg(-1)) for 4 h. Epinephrine treatment induced heat shock 70(Hsp70) expression in the stress responsive tissues, such as the cortex, hippocampus, thymus, and kidney. Further, the expression of thioredoxin-1(Trx-1), a cytoprotective protein, was also upregulated in these stress responsive tissues. In addition, the phosphorylation of cAMP-response element binding protein (CREB), a transcription factor of Trx-1, was increased after treatment with epinephrine. The block of CREB activation by H89 inhibited the acute epinephrine stress-induced Trx-1 and Hsp70 expression. Taken together, our data suggest that acute stimuli of epinephrine induced Trx-1 expression through activating CREB and may represent a protective role against stress.

Adrenaline release evokes hyperpnoea and an increase in ventilatory CO2 sensitivity during hypoglycaemia: a role for the carotid body.

KEY POINTS: Hypoglycaemia is counteracted by release of hormones and an increase in ventilation and CO2 sensitivity to restore blood glucose levels and prevent a fall in blood pH. The full counter-regulatory response and an appropriate increase in ventilation is dependent on carotid body stimulation. We show that the hypoglycaemia-induced increase in ventilation and CO2 sensitivity is abolished by preventing adrenaline release or blocking its receptors. Physiological levels of adrenaline mimicked the effect of hypoglycaemia on ventilation and CO2 sensitivity. These results suggest that adrenaline, rather than low glucose, is an adequate stimulus for the carotid body-mediated changes in ventilation and CO2 sensitivity during hypoglycaemia to prevent a serious acidosis in poorly controlled diabetes. ABSTRACT: Hypoglycaemia in vivo induces a counter-regulatory response that involves the release of hormones to restore blood glucose levels. Concomitantly, hypoglycaemia evokes a carotid body-mediated hyperpnoea that maintains arterial CO2 levels and prevents respiratory acidosis in the face of increased metabolism. It is unclear whether the carotid body is directly stimulated by low glucose or by a counter-regulatory hormone such as adrenaline. Minute ventilation was recorded during infusion of insulin-induced hypoglycaemia (8-17 mIU kg(-1)  min(-1) ) in Alfaxan-anaesthetised male Wistar rats. Hypoglycaemia significantly augmented minute ventilation (123 ± 4 to 143 ± 7 ml min(-1) ) and CO2 sensitivity (3.3 ± 0.3 to 4.4 ± 0.4 ml min(-1)  mmHg(-1) ). These effects were abolished by either ß-adrenoreceptor blockade with propranolol or adrenalectomy. In this hypermetabolic, hypoglycaemic state, propranolol stimulated a rise in P aC O2, suggestive of a ventilation-metabolism mismatch. Infusion of adrenaline (1 µg kg(-1)  min(-1) ) increased minute ventilation (145 ± 4 to 173 ± 5 ml min(-1) ) without altering P aC O2 or pH and enhanced ventilatory CO2 sensitivity (3.4 ± 0.4 to 5.1 ± 0.8 ml min(-1)  mmHg(-1) ). These effects were attenuated by either resection of the carotid sinus nerve or propranolol. Physiological concentrations of adrenaline increased the CO2 sensitivity of freshly dissociated carotid body type I cells in vitro. These findings suggest that adrenaline release can account for the ventilatory hyperpnoea observed during hypoglycaemia by an augmented carotid body and whole body ventilatory CO2 sensitivity.

The Epinephrine/Norepinephrine/Autoinducer-3 Interkingdom Signaling System in Escherichia coli O157:H7.

Epinephrine/norepinephrine/AI-3 signaling is used as an interkingdom chemical signaling system between microbes and their hosts. This system is also exploited by pathogens to regulate virulence traits. In enterohemorrhagic E. coli (EHEC) O157:H7, it is essential for pathogenesis and flagella motility. These three signals activate expression of a pathogenicity island named locus of enterocyte effacement (LEE), Shiga toxin, and the flagella regulon. These signals are sensed by the two-component system QseBC, whereas the bacterial membrane receptor QseC autophosphorylates and phosphorylates the QseB response regulator initiating a complex phosphorelay signaling cascade that activates the expression of a second two-component system, QseEF. The QseEF two-component system is also involved in the expression of the virulence genes, and it senses epinephrine, phosphate, and sulfate. This complex signaling cascade still needs to be completely elucidated.

Adrenaline rush: an unusual presentation of phaeochromocytoma.

A 44-year-old man presented to the accident and emergency department with chest pain and shortness of breath. Admission ECG revealed ischaemic changes. He had markedly elevated troponin T and a severely impaired left ventricular ejection fraction with regional motion wall abnormalities. He was initially treated in intensive care for acute myocardial infarction. When his renal function improved, an angiogram was performed, which showed unobstructed coronary arteries. He was later found to have a phaeochromocytoma. This case illustrates a rare diagnosis presenting with common symptoms that could easily have been missed. On admission to hospital, patients can easily be labelled with a diagnosis and put on a treatment pathway, such as acute coronary syndrome. It is important for clinicians to keep an open mind and be prepared to review the diagnosis if the history does not fit.

Biogenic amines at a low level of evolution: Production, functions and regulation in the unicellular Tetrahymena.

The unicellular eukaryote Tetrahymena synthesize, store and secrete biogenic amines (histamine, serotonin, epinephrine, dopamine, melatonin) and also can take up amines from the milieu. It also has (G-protein-coupled) receptors (binding sites) for these amines as well, as second messengers. The factors infuencing the mentioned processes are shown. For certain amines the genes and the coded enzymes are demonstrated. The amines influence phagocytosis, cell division, ciliary regeneration, glucose metabolism and chemotaxis. There are interhormone actions between the amines, and between the amines and other hormones produced by Tetrahymena. The critical review discusses the role of amines in the early stages of evolution and compares this to their functions in mammals. It tries to give answer how and why biogenic amines were selected to hormones, and why new functions formed for them in higher ranked animals, preserving also the ancient ones.

Peripheral and central effects of circulating catecholamines.

Physical challenges, emotional arousal, increased physical activity, or changes in the environment can evoke stress, requiring altered activity of visceral organs, glands, and smooth muscles. These alterations are necessary for the organism to function appropriately under these abnormal conditions and to restore homeostasis. These changes in activity comprise the "fight-or-flight" response and must occur rapidly or the organism may not survive. The rapid responses are mediated primarily via the catecholamines, epinephrine, and norepinephrine, secreted from the adrenal medulla. The catecholamine neurohormones interact with adrenergic receptors present on cell membranes of all visceral organs and smooth muscles, leading to activation of signaling pathways and consequent alterations in organ function and smooth muscle tone. During the "fight-or-flight response," the rise in circulating epinephrine and norepinephrine from the adrenal medulla and norepinephrine secreted from sympathetic nerve terminals cause increased blood pressure and cardiac output, relaxation of bronchial, intestinal and many other smooth muscles, mydriasis, and metabolic changes that increase levels of blood glucose and free fatty acids. Circulating catecholamines can also alter memory via effects on afferent sensory nerves impacting central nervous system function. While these rapid responses may be necessary for survival, sustained elevation of circulating catecholamines for prolonged periods of time can also produce pathological conditions, such as cardiac hypertrophy and heart failure, hypertension, and posttraumatic stress disorder. In this review, we discuss the present knowledge of the effects of circulating catecholamines on peripheral organs and tissues, as well as on memory in the brain.