Regulation of Norepinephrine Biosynthesis

Weiner, Norman

doi:10.1146/annurev.pa.10.040170.001421

Cited by 226 publications

(70 citation statements)

References 2 publications

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“…These observations confirm that the majority of the DA in the bowel is not of sympathetic origin because the concentration of DA does not decrease when the sympathetic nerves degenerate. The increased tissue content of DOPAC in the extrinsically denervated bowel is consistent with the idea that the turnover of DA increases after denervation, possibly because dopaminergic neurons become more active; however, as usually occurs when catecholaminergic neurons are stimulated, an increase in transmitter biosynthesis compensates for the stimulation-induced transmitter release to maintain near constancy in the stores of the transmitter (Weiner, 1970;Molinoff and Axelrod, 1971;Iuvone et al, 1978).…”

Section: Effects Of Extrinsic Denervation On Enteric Da and Dopacsupporting

confidence: 83%

Enteric Dopaminergic Neurons: Definition, Developmental Lineage, and Effects of Extrinsic Denervation

Li¹,

Pham²,

Tamir³

et al. 2004

J. Neurosci.

170

173

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The existence of enteric dopaminergic neurons has been suspected; however, the innervation of the gut by sympathetic nerves, in which dopamine (DA) is the norepinephrine precursor, complicates analyses of enteric DA. We now report that transcripts encoding tyrosine hydroxylase (TH) and the DA transporter (DAT) are present in the murine bowel (small intestine Ͼ stomach or colon; proximal colon Ͼ distal colon). Because sympathetic neurons are extrinsic, transcripts encoding TH and DAT in the bowel are probably derived from intrinsic neurons. TH protein was demonstrated immunocytochemically in neuronal perikarya (submucosal Ͼ Ͼ myenteric plexus; small intestine Ͼ stomach or colon). TH, DA, and DAT immunoreactivities were coincident in subsets of neurons (submucosal Ͼ myenteric) in guinea pig and mouse intestines in situ and in cultured guinea pig enteric ganglia. Surgical ablation of sympathetic nerves by extrinsic denervation of loops of the bowel did not affect DAT immunoreactivity but actually increased numbers of TH-immunoreactive neurons, expression of mRNA encoding TH and DAT, and enteric DOPAC (the specific dopamine metabolite). The fetal gut contains transiently catecholaminergic (TC) cells. TC cells are the proliferating crest-derived precursors of mature neurons that are not catecholaminergic and, thus, disappear after embryonic day (E) 14 (mouse) or E15 (rat). TC cells appear early in ontogeny, and their development/survival is dependent on mash-1 gene expression. In contrast, the intrinsic TH-expressing neurons of the murine bowel appear late (perinatally) and are mash-1 independent. We conclude that the enteric nervous system contains intrinsic dopaminergic neurons that arise from a mash-1-independent lineage of noncatecholaminergic precursors.

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Section: Effects Of Extrinsic Denervation On Enteric Da and Dopacsupporting

confidence: 83%

Enteric Dopaminergic Neurons: Definition, Developmental Lineage, and Effects of Extrinsic Denervation

Li¹,

Pham²,

Tamir³

et al. 2004

J. Neurosci.

170

173

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“…Sev eral hypotheses advocating multiple transmitter pools in dopaminergic terminals (Weiner, 1970;Ja voy and Glowinski, 1971;Westerink and Spaan, 1982;Nissbrandt and Carlsson, 1987) have been proposed. Some reports are consistent with a dif ference between the kinetic behavior of native DOPA and its radioactive tracers (Leviel et aI., 1989).…”

Section: Fdopa Modelmentioning

confidence: 99%

Human Striatal l-DOPA Decarboxylase Activity Estimated in vivo Using 6-[¹⁸F]fluoro-DOPA and Positron Emission Tomography: Error Analysis and Application to Normal Subjects

Kuwabara

Cumming

Reith

et al. 1993

J Cereb Blood Flow Metab

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Summary: DOPA decarboxylase is the enzyme directly responsible for the synthesis of the neurotransmitters do pamine and serotonin, and indirectly of noradrenaline, in brain. We used the decarboHlation coefficient (�) of 6-esp]fluoro-DOPA (PDOPA) to denote the relative ac tivity of L-DOPA decarboxylase in vivo in the human brain. To determine the relative enzyme activity with positron emission tomography (PET), we evaluated the model that separates the metabolism into compartments of nondiffusible and diffusible (i.e., transient) tracer me tabolites. Error analysis indicated that the least-squares optimization alone was not sufficient to yield accurate estimates of � in the presence of the inherent error of PET. To improve the accuracy of the kf estimates by optimizing the number of parameters, we introduced bi ological constraints which included a tracer partition vol-

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“…In support of this concept is the observation that an increase in the endogenous norepinephrine content of sympathetically innervated tissues by prior treatment with monoamine oxidase inhibitors results in a marked reduction of norepinephrine biosynthesis (9). In view of these as well as other observations, it has been suggested that the acceleration of norepinephrine biosynthesis that occurs during increased sympathetic activity results from the depletion of a small strategic pool of norepinephrine which releases tyrosine hydroxylase from negative feedback inhibition, thus causing an apparent activation of the enzyme (2,4,10). Consistent with the above hypothesis is the observation that synthesis and release appear to be intimately coupled.…”

mentioning

confidence: 70%

“…Since the discovery that tyrosine hydroxylases of both peripheral and central origin are inhibited by catecholamines (6,8), it has been speculated that noradrenergic neurons regulate the synthesis of their transmitter by means of end-product feedback inhibition of tyrosine hydroxylase (10). Thus, it has been argued that in the resting state tyrosine hydroxylase is partially inhibited in the nerve terminal by a small "strategic"…”

Section: Discussionmentioning

confidence: 99%

Tyrosine Hydroxylase: Activation by Nerve Stimulation

Morgenroth

Boadle-Biber

Roth

1974

Proc. Natl. Acad. Sci. U.S.A.

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The synthesis of the sympathetic neurotransmitter, norepinephrine, is accelerated by electrical stimulation of the guinea pig vas deferens. The molecular mechanism responsible for this enhanced formation of transmitter is unknown but has been attributed to an increase in the activity of tyrosine hydroxylase (EC 1.14.16.2; tyrosine 3-monooxygenase) during nerve stimulation. In the present experiments, we found that crude preparations of tyrosine hydroxylase isolated from guinea pig vasa deferentia that were electrically stimulated or depolarized by potassium show an increase in activity compared with enzyme obtained from untreated paired control tissues.

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Regulation of Norepinephrine Biosynthesis

Cited by 226 publications

References 2 publications

Enteric Dopaminergic Neurons: Definition, Developmental Lineage, and Effects of Extrinsic Denervation

Enteric Dopaminergic Neurons: Definition, Developmental Lineage, and Effects of Extrinsic Denervation

Human Striatal l-DOPA Decarboxylase Activity Estimated in vivo Using 6-[¹⁸F]fluoro-DOPA and Positron Emission Tomography: Error Analysis and Application to Normal Subjects

Tyrosine Hydroxylase: Activation by Nerve Stimulation

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Regulation of Norepinephrine Biosynthesis

Cited by 226 publications

References 2 publications

Enteric Dopaminergic Neurons: Definition, Developmental Lineage, and Effects of Extrinsic Denervation

Enteric Dopaminergic Neurons: Definition, Developmental Lineage, and Effects of Extrinsic Denervation

Human Striatal l-DOPA Decarboxylase Activity Estimated in vivo Using 6-[18F]fluoro-DOPA and Positron Emission Tomography: Error Analysis and Application to Normal Subjects

Tyrosine Hydroxylase: Activation by Nerve Stimulation

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Human Striatal l-DOPA Decarboxylase Activity Estimated in vivo Using 6-[¹⁸F]fluoro-DOPA and Positron Emission Tomography: Error Analysis and Application to Normal Subjects