THE UPTAKE OF CIRCULATING [<sup>3</sup>H]NOREPINEPHRINE BY THE PITUITARY GLAND AND VARIOUS AREAS OF THE BRAIN

Weil‐Malherbe, H.; Whitby, L. G.; Axelrod, Julius

doi:10.1111/j.1471-4159.1961.tb13526.x

Cited by 120 publications

(21 citation statements)

References 14 publications

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“…However, the direct action of these drugs on the median eminence and pituitary gland should not be disregarded because these areas are located outside the barrier. It was shown by Well Malherbe et al (42) that 2 min after a rapid intravenous injection, the pituitary gland contained radioactive nor epinephrine in high concentration, exceeding that in plasma. Direct action of epinephrine and norepinephrine in anterior pituitary cells in primary culture was also reported by Giguere et al (43,44).…”

Section: Discussionmentioning

confidence: 98%

Effect of α1- and α2-Adrenoceptor Agorists and Antagonists on ACTH Secretion in Intact and in Hypothalamic Deafferentated Rats

Shimizu

1984

Japanese Journal of Pharmacology

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Abstract-The effect of systemically injected a, and a2-adrenoceptor agonists and antagonists on ACTH secretion was studied in rats. Epinephrine, norepin ephrine, phenylephrine, clonidine, B-HT933, and B-HT920 caused a significant and dose-related increase of the ACTH concentration in the serum. The order of median effective dose (ED50) of these drugs on ACTH secretion was as follows: epinephrine norepinephrine < B-HT920 < clonidine < phenylephrine <; B-HT933. Isoproterenol, a ,3-adrenoceptor agonist, had no effect on ACTH secretion. ACTH secretion induced by epinephrine or phenylephrine was significantly inhibited by a-adrenoceptor antagonists, phentolamine and phenoxybenzamine. However, propranolol, a ;3-adrenoceptor antagonist, had no effect on ACTH secretion induced by epinephrine.Prazosin, an a,-antagonist, and yohimbine, an a2-antagonist, significantly blocked ACTH secretion induced by phenylephrine, an a,-agonist, and B-HT933, an a2-agonist, respectively.ACTH secretion induced by norepinephrine or a low dose of clonidine was inhibited by both prazosin and yohimbine.However, ACTH secretion induced by a high dose of clonidine was blocked only by prazosin. In rats with complete deafferentation of the medial basal hypothalamus (MBH), ACTH secretion induced by epinephrine, norepinephrine, and clonidine was sig nificantly blocked, as compared with intact rats. These results suggest that both peripheral a, and a2-adrenoceptors are involved in ACTH secretion induced by systemically injected adrenergic drugs in rats, and intact neural pathways entering the MBH are necessary for this ACTH releasing action.

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Section: Discussionmentioning

confidence: 98%

Effect of α1- and α2-Adrenoceptor Agorists and Antagonists on ACTH Secretion in Intact and in Hypothalamic Deafferentated Rats

Shimizu

1984

Japanese Journal of Pharmacology

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“…MAP-mediated SCBF increases were examined with use of phenylephrine which does not pass through the blood-brain barrier [17]. After intravenous administration of phenylephrine at doses which produced increases of MAP similar to those induced by pinching, SCBF showed significant increases.…”

Section: Pinching Increases Spinal Cord Blood Flowmentioning

confidence: 99%

Responses of Dorsal Spinal Cord Blood Flow to Noxious Mechanical Stimulation of the Skin in Anesthetized Rats

et al. 2008

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Abstract:In urethane-anesthetized, artificially ventilated rats, alterations in dorsal spinal cord blood flow (SCBF) at the L4-6 level were measured with laser Doppler flowmetry in response to noxious mechanical cutaneous stimulation (pinching) of either a forepaw or a hindpaw. The stimulation was delivered ipsilaterally or contralaterally to the site of blood flow measurement. Pinching of the forepaw or the hindpaw on either side increased mean arterial pressure (MAP) to the same degree. However, the SCBF response to pinching of the ipsilateral hindpaw was significantly greater than that to other stimulations. These responses were not influenced by denervation of the baroreceptors. The responses of SCBF to pinching of the ipsilateral hindpaw persisted both after treatment with phenoxybenzamine and after spinalization at the C1-2 level, whereas the responses to pinching at other sites disappeared. The responses of MAP to stimulation at all four sites became negligible after treatment with phenoxybenzamine and after spinalization at the C1-2 level. These results indicate that noxious mechanical stimulation of the skin produces increases in SCBF via two mechanisms: one is via an elevation of systemic arterial pressure; the other is via a localized spinal mechanism evoked by ipsilateral, segmental inputs.

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“…It has been known for many years that in addition to loss of nigrostriatal dopaminergic cells, PD entails loss of central NE-producing cells in the locus coeruleus (32,84,88) which is the main site of origin of noradrenergic fibers in the brain. Whereas catecholamines such as NE do not penetrate the blood-brain barrier (105,106) L-DOPS, as a neutral amino acid, would be expected to traverse the blood-brain barrier, potentially providing a prodrug that would increase delivery of NE to its receptors in the central nervous system and thereby alleviate effects of central NE deficiency. Consistent with the potential usefulness of L-DOPS as a central noradrenergic pro-drug, preclinical studies noted penetration of L-DOPS into the brain (71), minor but detectable increases in cerebrospinal fluid levels of NE (40) and in brain tissue levels of the NE metabolite 3-methoxy-4-hydroxyphenylglycol (48,90) after systemic L-DOPS administration, and reversal by L-DOPS of reserpine-induced ptosis and hypothermia (49,50).…”

Section: History Of L-dops Developmentmentioning

confidence: 99%

L‐Dihydroxyphenylserine (L‐DOPS): A Norepinephrine Prodrug

Goldstein

2006

Cardiovascular Drug Reviews

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L-threo-3,4-dihydroxyphenylserine (L-DOPS, droxydopa) is a synthetic catecholamino acid. When taken orally, L-DOPS is converted to the sympathetic neurotransmitter, norepinephrine (NE), via decarboxylation catalyzed by L-aromatic-amino-acid decarboxylase (LAAAD). Plasma L-DOPS levels peak at about 3 h, followed by a monoexponential decline with a half-time of 2 to 3 h. Plasma levels of NE and of its main neuronal metabolite, dihydroxyphenylglycol (DHPG) peak approximately concurrently but at much lower concentrations. The relatively long half-time for disappearance of L-DOPS from plasma, compared to that of NE, explains their very different attained plasma concentrations. In patients with neurogenic orthostatic hypotension, L-DOPS increases blood pressure and ameliorates orthostatic intolerance. Inhibition of LAAAD, such as by treatment with carbidopa, which does not penetrate the blood-brain barrier, prevents the blood pressure effects of the drug, indicating that L-DOPS increases blood pressure by augmenting NE production outside the brain. Patients with pure autonomic failure (which usually entails loss of sympathetic noradrenergic nerves), and patients with multiple system atrophy (in which noradrenergic innervation remains intact) have similar plasma NE responses to L-DOPS. This suggests mainly non-neuronal production of NE from L-DOPS. L-DOPS is very effective in treatment of deficiency of dopamine-beta-hydroxylase (DBH), the enzyme required for conversion of dopamine to NE in sympathetic nerves. L-DOPS holds promise for treating other much more common conditions involving decreased DBH activity or NE deficiency, such as a variety of syndromes associated with neurogenic orthostatic hypotension.

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THE UPTAKE OF CIRCULATING [³H]NOREPINEPHRINE BY THE PITUITARY GLAND AND VARIOUS AREAS OF THE BRAIN

Cited by 120 publications

References 14 publications

Effect of α1- and α2-Adrenoceptor Agorists and Antagonists on ACTH Secretion in Intact and in Hypothalamic Deafferentated Rats

Effect of α1- and α2-Adrenoceptor Agorists and Antagonists on ACTH Secretion in Intact and in Hypothalamic Deafferentated Rats

Responses of Dorsal Spinal Cord Blood Flow to Noxious Mechanical Stimulation of the Skin in Anesthetized Rats

L‐Dihydroxyphenylserine (L‐DOPS): A Norepinephrine Prodrug

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THE UPTAKE OF CIRCULATING [3H]NOREPINEPHRINE BY THE PITUITARY GLAND AND VARIOUS AREAS OF THE BRAIN

Cited by 120 publications

References 14 publications

Effect of α1- and α2-Adrenoceptor Agorists and Antagonists on ACTH Secretion in Intact and in Hypothalamic Deafferentated Rats

Effect of α1- and α2-Adrenoceptor Agorists and Antagonists on ACTH Secretion in Intact and in Hypothalamic Deafferentated Rats

Responses of Dorsal Spinal Cord Blood Flow to Noxious Mechanical Stimulation of the Skin in Anesthetized Rats

L‐Dihydroxyphenylserine (L‐DOPS): A Norepinephrine Prodrug

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THE UPTAKE OF CIRCULATING [³H]NOREPINEPHRINE BY THE PITUITARY GLAND AND VARIOUS AREAS OF THE BRAIN