Distribution of adrenaline-synthesizing enzyme activity in the human brain

doi:10.1016/0022-510X(79)90098-4

Journal of the Neurological Sciences

Volume 41, Issue 3, May 1979, Pages 397-409

https://doi.org/10.1016/0022-510X(79)90098-4 Get rights and content

Abstract

A study of the distribution of phenylethanolamine-N-methyl-transferase (PNMT) activity in normal human brain is presented. After a preliminary dissection to separate brain tissue for formalin fixation and tissue designed for biochemical studies, the hemi-brain stem is cut in slices by hand and a cerebral hemisphere is cut on a cryomicrotome. “Punches” are made with an operating microscope. This dissection method was used to study the distribution of PNMT activity in 117 “punches” made on 21 slices obtained from 5 normal human brains. The caudo-rostral distribution of PNMT activity in C1 and C2 groups was found to be identical in each brain. The distribution of PNMT activity was found to be similar to that in the rat, but, in addition, important activity was found in the substantia nigra, internal pallidum and nucleus accumbens.

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Cited by (42)

Normative data of dopaminergic neurotransmission functions in substantia nigra measured with MRI and PET: Neuromelanin, dopamine synthesis, dopamine transporters, and dopamine D<inf>2</inf> receptors
2017, NeuroImage
Citation Excerpt :
In the present study, high uptake of L-[β-11C]DOPA was observed in periaqueductal gray matter. Norepinephrine is synthesized from dopamine in periaqueductal gray matter (Kopp et al., 1979; Mefford et al., 1977), and the precursor of dopamine, l-DOPA, is observed in this region (Kitahama et al., 2007). Thus, periaqueductal gray matter containing norepinephrinergic neurons showed high uptake of L-[β-11C]DOPA.
The central dopaminergic system is of major importance in the pathophysiology of Parkinson's disease, schizophrenia, and other neuropsychiatric disorders. In the present study, the normative data of dopaminergic neurotransmission functions in the midbrain, consisting of neuromelanin, dopamine synthesis, dopamine transporters and dopamine D₂ receptors, were constructed using magnetic resonance (MR) imaging and positron emission tomography (PET). PET studies with L-[β-¹¹C]DOPA, [¹⁸F]FE-PE2I and [¹¹C]FLB457 and MRI studies were performed on healthy young men. Neuromelanin accumulation measured by MRI was compared with dopaminergic functions, dopamine synthesis capacity, dopamine transporter binding and dopamine D₂ receptor binding measured by PET in the substantia nigra. Although neuromelanin is synthesized from DOPA and dopamine in dopaminergic neurons, neuromelanin accumulation did not correlate with dopamine synthesis capacity in young healthy subjects. The role of dopamine transporters in the substantia nigra is considered to be the transport of dopamine into neurons, and therefore dopamine transporter binding might be related to neuromelanin accumulation; however, no significant correlation was observed between them. A positive correlation between dopamine D₂ receptor binding and neuromelanin accumulation was observed, indicating a feedback mechanism by dopaminergic autoreceptors. Discrepancies in regional distribution between neuromelanin accumulation and dopamine synthesis capacity, dopamine transporter binding or dopamine D₂ receptor binding were observed in the substantia nigra.
Periaqueductal Gray
2012, The Human Nervous System, Third Edition
A putative morphological substrate of the catecholamine-influenced neuropeptide Y (NPY) release in the human hypothalamus
2011, Neuropeptides
Citation Excerpt :
Since formaldehyde-induced fluorescence (Dahlstrom and Fuxe, 1964) and tyrosine hydroxylase (TH) immunoreactivity cannot differentiate between dopaminergic, epinephrinergic and norepinephrinergic structures, the presence of key, rate-limiting enzymes of catecholamine synthesis is used to differentiate between the different types of catecholaminergic elements. Dopamine-beta hydroxylase (DBH) is located in both adrenergic and noradrenergic neurons, therefore, the presence of phenylethanolamine N-methyltransferase (PNMT), the rate-limiting enzyme of the adrenaline synthesis, is used to identify the adrenergic elements in the brain of several species including human by using immunohistochemistry (Ericson et al., 1989; Mezey, 1989; Palkovits et al., 1992) and enzyme activity assays (Kopp et al., 1979; Lew et al., 1977; Moreno et al., 1992; Nagatsu et al., 1977). In the present study, we examined the putative juxtapositions between the catecholaminergic and NPY-IR neurons.
Neuropeptide Y (NPY) is a 36 amino acid peptide, which among others, plays a pivotal role in stress response. Although previous studies confirmed that NPY release is increased by stress in several species, the exact mechanism of the stress-induced NPY release has not been elucidated yet.
In the present study, we examined, with morphological means, the possibility that catecholamines directly influence NPY release in the human hypothalamus. Since the use of electron microscopic techniques is virtually impossible in immunostained human samples due to the long post mortem time, double-label immunohistochemistry was utilised in order to reveal the putative catecholaminergic-NPY associations.
The present study is the first to demonstrate juxtapositions between the catecholaminergic, tyrosine hydroxylase (TH)/dopamine-beta hydroxylase (DBH)-immunoreactive (IR) and NPY-IR neural elements in the human hypothalamus. These en passant type associations are most numerous in the infundibular and periventricular areas of the human diencephalon. Here, NPY-IR neurons often form several contacts with catecholaminergic fibre varicosities, without any observable gaps between the contacting elements, suggesting that these juxtapositions may represent functional synapses. The lack of phenylethanolamine N-methyltransferase (PNMT)-NPY juxtapositions and the relatively few observed DBH-NPY associations suggest that the vast majority of the observed TH-NPY juxtapositions represent dopaminergic synapses. Since catecholamines are known to be the crucial components of the stress response, the presence of direct, catecholaminergic (primarily dopaminergic)-NPY-IR synapses may explain the increased NPY release during stress. The released NPY in turn is believed to play an active role in the responses that are directed to maintain the homeostasis during stressful conditions.
Distribution and morphology of the catecholaminergic neural elements in the human hypothalamus
2010, Neuroscience
Previous studies have demonstrated that catecholaminergic, tyrosine hydroxylase (TH)-immunoreactive (IR) perikarya and fibers are widely distributed in the human hypothalamus. Since TH is the key and rate-limiting enzyme for catecholaminergic synthesis, these IR neurons may represent dopaminergic, noradrenergic or adrenergic neural elements. However, the distribution and morphology of these neurotransmitter systems in the human hypothalamus is not entirely known. Since the different catecholaminergic systems can be detected by identifying the neurons containing the specific key enzymes of catecholaminergic synthesis, in the present study we mapped the catecholaminergic elements in the human hypothalamus using immunohistochemistry against the catecholaminergic enzymes, TH, dopamine beta-hydroxylase (DBH) and phenylethanolamine-N-methyltransferase (PNMT). Only a few, PNMT-IR, adrenergic neuronal elements were found mainly in the infundibulum and the periventricular zone. DBH-IR structures were more widely distributed in the human hypothalamus occupying chiefly the infundibulum/infundibular nucleus, periventricular area, supraoptic and paraventricular nuclei. Dopaminergic elements were detected by utilizing double label immunohistochemistry. First, the DBH-IR elements were visualized; then the TH-IR structures, that lack DBH, were detected with a different chromogen. In our study, we conclude that all of the catecholaminergic perikarya and the majority of the catecholaminergic fibers represent dopaminergic neurons in the human hypothalamus. Due to the extremely small number of PNMT-IR, adrenergic structures in the human hypothalamus, the DBH-IR fibers represent almost exclusively noradrenergic neuronal processes. These findings suggest that the juxtapositions between the TH-IR and numerous peptidergic systems revealed by previous reports indicate mostly dopaminergic synapses.
Labetalol facilitates GABAergic transmission to rat periaqueductal gray neurons via antagonizing β<inf>1</inf>-adrenergic receptors - A possible mechanism underlying labetalol-induced analgesia
2008, Brain Research
Citation Excerpt :
Several lines of evidence point to the possibility that norepinephrine functions within the PAG. 1) Both catecholamine-synthesizing enzymes: tyrosine hydroxylase (Pearson et al., 1983) and the norepinerphrine-synthesizing phenylethanolamine N-methyltransferase (Kopp et al., 1979) are expressed in the PAG. 2) Release-based studies have shown high concentrations of norepinephrine in the PAG (Behbehani, 1995).
Labetalol, a combined α₁, β₁, and β₂ adrenoceptor-blocking drug, has been shown to have analgesic properties in vivo. To determine the underlying mechanisms, we examined its effects on GABA_A receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) and spontaneous firings of rat ventrolateral periaqueductal gray (PAG) neurons, either mechanically dissociated, or in acute brain slices. These PAG neurons mediate opioid-mediated analgesia and pain transmission and are under tonic control of GABAergic interneurons. An increase in GABAergic transmission to these neurons yields an inhibitory hyperpolarized state and may interrupt pain signal transmission. Using patch clamp techniques, we found that labetalol reversibly increases the frequency of sIPSCs without changing their mean amplitude. This indicates that labetalol enhances GABAergic synaptic transmission by a presynaptic mechanism. Metoprolol, a specific β₁-adrenoceptor antagonist, also reversibly enhanced sIPSC frequency. In the presence of metoprolol, labetalol-induced increase in sIPSC frequency was significantly attenuated or even abolished. These results suggest that labetalol shares the same pathway as metoprolol in enhancing GABAergic transmission via an inhibition of presynaptic β₁-adrenoceptors. We further showed that labetalol reversibly reduced the firing rate of PAG neurons. This reduction was significantly attenuated in the presence of bicuculline, a selective antagonist of GABA_A receptors. These data indicate that labetalol-induced inhibition of PAG cell firing is attributable to its potentiation of GABAergic transmission. Based on these data, we postulate that labetalol-induced analgesia is at least in part ascribed to its antagonistic effects on presynaptic β₁-adrenoceptors.
Periaqueductal Gray
2003, The Human Nervous System: Second Edition

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^☆: This work was supported by a grant (ATP 657897) from INSERM.

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Distribution of adrenaline-synthesizing enzyme activity in the human brain☆

Abstract

Brain Res.

Brain Res.

J. biol. Chem.

Neurosci. Lett.

Clin. chim. Acta

Brain Res.

Brain Res.

Regional distribution of choline acetyltransferase in the human brain — Changes in Huntington's chorea

J. Neurol. Neurosurg. Psych.

Über die Kerngebiete des menschlichen Hirnstammes, Part 2 (Die Raphékerne)

Z. Zellforsch.