Adrenaline and Noradrenaline: Partners and Actors in the Same Play (original) (raw)
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Catecholamines: Knowledge and understanding in the 1960s, now, and in the future
Brain and Neuroscience Advances, 2019
The late 1960s was a heyday for catecholamine research. Technological developments made it feasible to study the regulation of sympathetic neuronal transmission and to map the distribution of noradrenaline and dopamine in the brain. At last, it was possible to explain the mechanism of action of some important drugs that had been used in the clinic for more than a decade (e.g. the first generation of antidepressants) and to contemplate the rational development of new treatments (e.g. l-dihydroxyphenylalanine therapy, to compensate for the dopaminergic neuropathy in Parkinson’s disease, and β1-adrenoceptor antagonists as antihypertensives). The fact that drug targeting noradrenergic and/or dopaminergic transmission are still the first-line treatments for many psychiatric disorders (e.g. depression, schizophrenia, and attention deficit hyperactivity disorder) is a testament to the importance of these neurotransmitters and the research that has helped us to understand the regulation of ...
Historical Landmarks in the Discovery of Adrenal Hormones
World Journal of Endocrine Surgery
urinary excretion of the sodium-24 isotope in adrenalectomized rats. He approached separately to two specialists in the field of bioassay and radioisotope-Sylvia Agnes Sophia Tait and James Francis Tait (Fig. 3). 5 Later, they succeeded in developing a bioassay by measuring the effect of adrenal steroids on urinary excretion of radioisotopes of sodium-24 and potassium-42 in adrenalectomized rats. 6 This method paved the way for further discoveries of adrenal gland products. They also discussed the methods of isolation, biochemistry, and physiology of electrocortin. In 1952, they partnered with a Swiss Chemist, Professor Tadeus Reichstein, and were able to demonstrate the structure of electrocortin. 6 Later, Reichstein demonstrated the steroid nature of the electrocortin, and renamed the compound "aldosterone." 7 Glucocorticoids In January 1931, Dr Leonard G Rowntree of the Mayo Clinic demonstrated the efficacy of adrenal cortex extract in reducing the symptoms of Addison's disease in a patient. After knowing Edward Calvin Kendall's (Fig.
Biochemical Pharmacology, 1970
The exocytosis hypothesis for neurotransmitter release from sympathetic nerves was experimentally tested by studying the effect of nerve stimulation on the outflow of adenine nucleotide material from the cat spleen, and by comparing the adenine nucleotide content of stimulated and control portions of the splenic capsule. The adrenal medulla was used as a reference organ, assumed to secrete by exocytosis. The method used involved labelling the adenine nucleotides of the catecholamine storage particles in sympathetic nerves and adrenal medulla by daily injections of radioactive orthophosphate (32p) for one week. Results obtained by sucrose density gradient centrifugation and analysis by anion exchange column chromatography indicated that the technique used had resulted in significant labelling of the adenine nucleotides of the adrenal medullary amine storage particles, which have previously proved to be highly resistant to labelling with 32p. Induction of secretion in the perfused adrenal by carbachol consistently resulted in a largely parallel increase in cateeholamines and a2P-labelled material in the effluent from the gland. Chromatographic analysis showed that the labelled material consisted mainly of inorganic phosphate, with only small amounts of AMP and no ADP or ATP. In the splenic peffusion experiments contraction of the organ, whether induced by injection of angiotensin or by nerve stimulation, resulted in increased outflow of 32P-labelled material, exclusively as inorganic phosphate. However, when contraction was blocked by phenoxybenzamine, nerve stimulation caused a large rise in noradrenaline outflow, but had no effect on the level of saP-labelled material in the effluent. Moreover, prolonged nerve stimulation, known to cause release of about one half of the noradrenaline in the spleen, did not in any way affect the content of labelled adenine nucleotides of the splenic capsule. The present findings appear to be compatible with the exocytosis hypothesis for hormone secretion from the adrenal medulla, but they do not support the same hypothesis for neurotransmitter release from sympathetic nerves.
Pharmacology of Adrenaline, Noradrenaline, and Their Receptors
2020
Adrenaline and noradrenaline are important catecholamines of the biological system, responsible for the regulation of major functions of the body via their action on the brain. This noradrenaline is the chief neurotransmitter of the sympathetic nervous system, whereas adrenaline is an important metabolic hormone, known to play a vital role in the cardiovascular system and a mediator of the fight-or-flight response. These catecholamines act in the system through the membrane-bound GPCRs, adrenergic receptors (ARs). Two major classes of ARs, α-ARs and β-ARs, facilitate a number of functions at central and peripheral sites. There are two subtypes of α-ARs (α1-AR and α2-AR), whereas three different subtypes of β-ARs have been identified-β1-AR, β2-AR, and β3-AR. Based on their role, different AR modulators have been introduced clinically for their therapeutic application. In this chapter, we focus on the pharmacology of the two catecholamines through their action on different ARs within the biosystem
Long-term application of some catecholamines elevates levels of other catecholamines in rats
Experimental pathology, 1985
Male Sprague-Dawley rats were treated during 20 h with subcutaneously implanted tablets (controlled release systems) containing either adrenaline (A), noradrenaline (NA), isoprenaline (ISO) or just placebos. Levels of the exogenously administered catecholamines (CA) in plasma and liver homogenate were significantly higher than in controls throughout the test time. During NA application endogeneous A and dopamine (DA) plasma values rose considerably, while ISO application enhanced endogenous NA and A levels. Adrenaline application increased NA and DA plasma levels. Several possibilities for this phenomenon are discussed, and it is concluded that previous papers dealing with observations of long term action of CA's should be reevaluated unless the influence of the artificially given CA on the elevation of endogenous CA's has been already taken into consideration.
Direct stimulant effect of aminophylline on catecholamine release from the adrenal medulla
Biochemical Pharmacology, 1973
Bovine adrenal glands, perfused in vitro, responded to single injections or continuous infusions of aminophylline by increased release of catecholamines. This effect was not mediated by the release of acetylcholine in the gland, since it was not blocked by cholinergic blocking agents. Stimulation for short periods of time (4 min or less) showed that the catecholamine release was depressed when cxtracellular calcium was reduced; however, even in the absence of calcium, aminophylline still evoked catecholamine release. The stimulant effect of aminophylline was present during perfusion with high potassium media and was inhibited by the local anesthetic, dibucaine. Papaverine potentiated the response to aminophylline. The results are discussed in terms of two different mechanisms for aminophylline-induced secretion, one dependent on influx of extracellular calcium, and one dependent on release of intracellular calcium.
The inhibition in vivo of norepinephrine synthesis by adrenalone
Biochemical Pharmacology, 1962
THE BIOGENESIS of norepinephrine involves the oxidation of phenylalanine to tyrosine followed by hydroxylation to 3,4_dihydroxyphenylalanine, decarboxylation to dopamine (3,4_dihydroxyphenylethylamine) and ,%hydroxylation of dopamine to norepinephrine. The rate-limiting step in this reaction sequence may be the conversion of dopamine to norepinephrine, and the inhibition of dopamine-&hydroxylation may produce lower levels of norepinephrine and consequently higher levels of dopamine. The enzyme that catalyses the conversion of dopamine to norepinephrine was isolated from bovine adrenal medulla1 and it was shown not to be specific for dopamine. In view of this finding the enzyme was named phenylamine-ghydroxylase. a Many compounds were tested as possible inhibitors of the conversion of dopamine to norepinephrine by the hydroxylating enzyme.* Among the compounds thus far tested, adrenalone was the most effective in vitro." At a concentration of the substrate, dopamine, of 2 ~moles/ml, the formation of norpinephrine in a standard incubation mixture at pH 6-4 is i~ibited approxi~tely 50 per cent by adrenalone in a concentration of @2 pmoles/ ml. At lower pHs, the inhibition by adrenalone decreases sharply. A Lineweaver-Burk plot revealed that the inhibition by adrenalone is not of a competitive nature. The effective inhibition in vitro of norepinephrine synthesis by adrenalone at physiological pHs suggests that this compound may also be active in vivo. The inhibition in viva was investigated by a comparison of the content of norepinephrine-H3 formed from dopamine-Ii3 in several organs of rabbits treated and untreated with adrenalone. Each rabbit was treated with 100 mg iproniazid/kg 16 hr before the infusion of dopamine-HS. The adrenalone-treated rabbits received 4 mg adrenalone/kg i.p. both 12 hr and 1 hr before the infusion and, in addition, 2 mg/kg i.v. during the infusion of dopamine-H3; 0.2 mg of dopamine-a-H*, with the specific activity 10s cpm/mg, in a 20-ml solution was infused during a period of 20 min into the rabbit's ear vein. The rabbits were killed one hr after the infusion, The liver, heart, and spleen were removed and homogenized, and the homogenate was deproteinized with 5% trichloracetic acid. After centrifugation the acid metabolites of dopamine and the excess of trichloracetic acid were removed by extraction three times with an equal volume of ethylacetate. The aqueous phase was adjusted to pH4 and the amines were acetyiated as previously described.* The acetylated amines were chromatographed in the "c" solvent system of Bush, and the dry chromatograms were scanned for radioactive zones. The radiochromatograms obtained from the spleen of the rabbits treated and untreated with adrenalone are presented in Fig. 1. It is evident that in the spleen of the adrenalone-treated rabbit the content of no~inephrine-H3 is decreased and the content of dopamine-HB is increased, as compared with the control. The radi~hromato~~s obtained from the hearts and livers of adrenalonetreated rabbits also show a decrease in the norepinephrine-Ha and an increase in the dopamine-Hs content, as compared with the controls. Upon elution of the corresponding radioactive peaks, the amounts of norepinephrine-Ha and dopamine-II" in each organ were determined in a Packard liquid scintillation spectrometer. Table 1 shows that the content of norepinephrine-H3 is decreased approximately 50 per cent in the heart and spleen of adrenalone-treated animals. The content of dopamineHs is increased almost to the same extent in these organs. The inhibition of norep~ep~~e synthesis by adrenalone in the liver is less effective. The results given in Table 1 are averages of three experiments.
Excretion of catecholamines in rats, mice and chicken
Journal of Comparative Physiology B, 2008
Stress assessment favours methods, which do not interfere with an animal's endocrine status. To develop such non-invasive methods, detailed knowledge about the excretion of hormone metabolites in the faeces and urine is necessary. Our study was therefore designed to generate basic information about catecholamine excretion in rats, mice and chickens. After administration of 3 H-epinephrine or 3 H-norepinephrine to male and female rats, mice and chickens, all voided excreta were collected for 4 weeks, 3 weeks or for 10 days, respectively. Peak concentrations of radioactivity appeared in one of the Wrst urinary samples of mice and rats and in the Wrst droppings in chickens 0.2-7.2 h after injection. In rats, between 77.3 and 95.6% of the recovered catecholamine metabolites were found in the urine, while in mice, a mean of 76.3% were excreted in the urine. Peak concentrations in the faeces were found 7.4 h post injection in mice, and after about 16.4 h in rats (means). Our study provides valuable data about the route and the proWle of catecholamine excretion in three frequently used species of laboratory animals. This represents the Wrst step in the development of a reliable, non-invasive quantiWcation of epinephrine and norepinephrine to monitor sympatho-adrenomedullary activity, although promising results for the development of a non-invasive method were found only for the chicken.