Catecholamine

About: Catecholamine is a research topic. Over the lifetime, 10753 publications have been published within this topic receiving 379056 citations. The topic is also known as: catecholamines.

Intricate Regulation of Tyrosine Hydroxylase Activity and Gene Expression

Abstract: Tyrosine hydroxylase catalyzes the rate-limiting step in the biosynthesis of the catecholamines dopamine, norepinephrine, and epinephrine. Therefore, the regulation of tyrosine hydroxylase enzyme number and intrinsic enzyme activity represents the central means for controlling the synthesis of these important biogenic amines. An intricate scheme has evolved whereby tyrosine hydroxylase activity is modulated by nearly every documented form of regulation. Beginning with the genomic DNA, evidence exists for the transcriptional regulation of tyrosine hydroxylase mRNA levels, alternative RNA processing, and the regulation of RNA stability. There is also experimental support for the role of both translational control and enzyme stability in establishing steady-state levels of active tyrosine hydroxylase protein. Finally, mechanisms have been proposed for feedback inhibition of the enzyme by catecholamine products, allosteric modulation of enzyme activity, and phosphorylation-dependent activation of the enzyme by various different kinase systems. Given the growing literature suggesting that different tissues regulate tyrosine hydroxylase mRNA levels and activity in different ways, regulatory mechanisms provide not only redundancy but also diversity in the control of catecholamine biosynthesis.

Elevated sympathetic nerve activity in borderline hypertensive humans. Evidence from direct intraneural recordings.

Abstract: Reports of elevated plasma catecholamine levels and augmented responses to autonomic blockade suggest increased sympathetic tone in borderline hypertension. It is not known if this reflects greater sympathetic neural outflow. We directly recorded muscle sympathetic nerve activity (microneurography) in 15 normotensive and 12 borderline hypertensive age-matched men to determine whether borderline hypertensive individuals have elevated sympathetic nerve activity. Supine heart rate, blood pressure, plasma norepinephrine, and efferent muscle sympathetic nerve activity (peroneal nerve) were measured after 6 days of both low and high dietary sodium intake (10 and 400 meq sodium/24 hr). Sympathetic nerve activity was elevated significantly in borderline hypertensive individuals on both low (37 +/- 1 in borderline hypertensive individuals vs. 29 +/- 1 bursts/min in normotensive individuals; p less than 0.01) and high (25 + 1 in borderline hypertensive individuals vs. 16 +/- 1 bursts/min in normotensive individuals; p less than 0.01) sodium diets. The borderline hypertensive group had higher systolic (p less than 0.01) and diastolic (p less than 0.05) blood pressures independent of sodium intake. Across both groups, high sodium intake reduced muscle sympathetic nerve activity (p less than 0.001), plasma norepinephrine (p less than 0.001), diastolic blood pressure (p less than 0.02), heart rate (p less than 0.002), and increased weight (p less than 0.005). A significant (p less than 0.05) group-by-diet interaction was observed for plasma norepinephrine levels. Specifically, compared with the normotensive group, plasma norepinephrine levels in the borderline hypertensive group tended to be higher on low sodium diet (p = 0.08) and lower on high sodium diet (p = 0.23).(ABSTRACT TRUNCATED AT 250 WORDS)

The hypoxia-responsive transcription factor EPAS1 is essential for catecholamine homeostasis and protection against heart failure during embryonic development

Abstract: Mice lacking the hypoxia-inducible transcription factor EPAS1 die at mid-gestation. Despite normal morphological development of the circulatory system, EPAS1-deficient mice display pronounced bradycardia. In addition to the vascular endothelium, EPAS1 is expressed intensively in the organ of Zuckerkandl (OZ), the principle source of catecholamine production in mammalian embryos. EPAS1-deficient embryos contained substantially reduced catecholamine levels. Mid-gestational lethality was rescued by administration of the catecholamine precursor DOPS to pregnant females. We hypothesize that EPAS1 expressed in the OZ senses hypoxia during mid-gestational development and translates this signal into an altered pattern of gene expression, leading to increases in circulating catecholamine levels and proper cardiac function.

Precursor control of neurotransmitter synthesis.

Abstract: Studies performed during the past decade have shown that the rates at which certain neurons produce and release their neurotransmitters can be affected by precursor availability, and thus by the changes in plasma composition that occur after ingestion of the precursors in purified form or as constituents of foods. Thus, tryptophan administration or a plasma ratio of tryptophan to other large neutral amino acids, thereby raising brain tryptophan levels, increasing the substrate saturation of tryptophan hydroxylase, and accelerating the synthesis and release of serotonin. Tyrosine administration or a high-protein meal similarly elevates brain tyrosine and can accelerate catecholamine synthesis in the CNS and sympathoadrenal cells, while the consumption of lecithin or choline increases brain choline levels and neuronal acetylcholine synthesis. The physiologic and biochemical mechanisms that must exist in order for nutrient consumption to affect neurotransmitte synthesis have been characterized and include: 1) the lack of significant feedback control of plasma levels of the precursor; 2) the lack of a real "bloodbrain barrier" for the precursor, i.e. the ability of the plasma level of the precursor to control its influx into, or efflux from, the CNS; 3) the existence of a low-affinity (and thus unsaturated) transport system mediating the flux of the precursor between blood and brain; 4) low-affinity kinetics for the enzyme that initiates the conversion of the precursor to the transmitter; and, 5) the lack of end-product inhibition of the enzyme, in vivo, by its ultimate product, the neurotransmitter. The extent to which neurotransmitter synthesis in any particular aminergic neuron happens to be affected by changes in the availability of its precursor probably varies directly with the neuron's firing frequency. This relationship allows precursor administration to produce selective physiologic effects by enhancing neurotransmitter release from some but not all of the neurons potentially capable of utilizing the precursor for this purpose. It also allows the investigator to predict when administering the precursor might be useful for amplifying a physiologic process, or for treating a pathologic state. (for example, tyrosine administration raises blood pressure in hypotensive rats, lowers it in hypertensive animals, and has little effect on blood pressure in normotensive animals; the elevation in blood pressure probably reflects enhanced catecholamine release from sympathoadrenal cells, while the reduction in hypertensive animals probably results from increased catecholamine release within the brain-stem.) Such predictions are now being tested clinically in many institution. Available evidence suggests that lecithin or cholie administration can diminish the frequency of abnormal movements in patients with tardive dyskinesia...

Assessment of human sympathetic nervous system activity from measurements of norepinephrine turnover.

Abstract: SINCE the sympathetic nervous system has such a central place in homeostasis in general, and in circulatory adaptation in particular, it is paradoxical that so little is known about the possible contribution of disturbed sympathetic nervous function to the development of human diseases. Clinical tests of sympathetic nervous system activity have, by and large, been routinely applied in one setting only: the detection of sympathetic nervous failure, from autonomic insufficiency syndromes, in patients with postural hypotension. A list of \"candidate\" diseases for sympathetic nervous system dysfunction might include, for example, essential hypertension, cardiac failure, coronary artery spasm, cirrhosis, mitral valve prolapse, and Raynaud's syndrome. Until very recently, the picture of sympathetic nervous pathophysiology for conditions such as these was particularly sketchy, mainly because of the rudimentary nature of the tests of sympathetic nervous system function available to investigative clinical medicine. Pertinent questions have gone incompletely answered at best — questions such as: Is the sympathetic nervous system directly involved in the early pathogenesis of essential hypertension? Is increased renal sympathetic activity a common cause of sodium retention in edematous states? Is increased cardiac sympathetic nerve firing an important element in the development of cardiac arrhythmias in humans?