3H-Norepinephrine

Azzaro, A.J., Ziance, R.J., and Rutledge, C.O., The importance of neuronal uptake of amines for amphetamine-induced release of 3H-norepinephrine from isolated brain tissue,. /. Pharmacol. Exp. Ther., 189, 110, 1974. 

Westfall, T.C., Effect of nicotine and other drugs on the release of 3H-norepinephrine and 3H-dopamine from rat brain slices, Neuropharmacology, 13, 693, 1974. 

Snyder, S.H., Coyle, J.T. Regional differences in 3H-norepinephrine and 3H-dopamine uptake into rat brain homogenates. J. Pharmacol. Exp. Ther. 165 78, 1969. 

Cameron OG, Smith CB Comparison of acute and chronic lithium treatment on 3H-norepinephrine uptake by rat brain slices. Psychopharmacology 67 81-85, 1980... 

EGb inhibits the uptake of [3H]norepinephrine ([3H]NE) and [3H]dopamine and [3H]5-hydroxytryptamine ([3H]5-HT) into in vitro synaptosomes prepared from the striatum and cortex in a concentration-dependent manner. The rank order of potency for the inhibition of amine uptake is NE > dopamine > 5-HT [173]. Similar results were obtained by Ramassamy et al. [174]. These workers showed that EGb decreased the specific uptakes of [3H]dopamine, [3H]5-HT and [3H]choline by synaptosomes prepared from the striatum of mice in a concentration-dependent manner. The IC,0 values were 637 pg/rol for [3H]dopamine uptake, 803 pg/ml for [3H]5-HT uptake, >2000 pg/ml for [3H]choline uptake. However, they concluded that the inhibition of amine uptake caused by EGb appears to be non-specific, since EGb also prevents the specific binding of the dopamine uptake inhibitor [3H]GBR12783 to membranes prepared from striatum. 

C.K. Kellogg and T.M. Retell, Release of (3H]norepinephrine Alteration by early developmental exposure to diazepam, Brain Res., 366 (1986) 137-144. 

Azam L, McIntosh JM (2006) Characterization of nicotinic acetylcholine receptors that modulate nicotine-evoked [3H]norepinephrine release from mouse hippocampal synaptosomes. Mol Pharmacol 70 967-76... 

A very intriguing observation noted above was the possibility of presynaptic dopamine agonist activity with SK F 87516 and SK F 85174. The inhibitions of the constrictor response and the 3H -norepinephrine release induced by brief intermittent periarterial sympathetic nerve stimulation of the perfused rabbit ear artery is a convenient in vitro assay for presynaptic dopamine agonist activity (30). In this preparation, both SK F 85174 and SK F 87516 inhibited both stimulation responses with an EC50 of about 100 riM. Another measure of D-2 activity is inhibition of specific spiroperidol binding (20). Comparison of these data (Table I) showed that SK F 85174 is thirty times as potent as dopamine, and thus is a potent D-2 agonist. However, the activity in adenylate cyclase stimulation indicates that this compound may be best described as a D-l/D-2 agonist (19, 20). 

In wild-type atrial preparations, increasing concentrations of the nonselective a2-AR agonist UK-14,304 dose dependently inhibited electrically-stimulated [3H]norepinephrine release (21). Consistent with previous studies, a2A-AR ablation did not completely attenuate the effects of UK-14,304 in suppressing [3H]norepinephrine release. In contrast, atrial preparations derived from o ac-AR 7 mice were completely unresponsive to UK-14,304 in this functional assay. Additional studies revealed that the o a-AR and o c-AR subtypes serve distinct roles in the regulation of neurotransmitter release (Table 1). Frequency inhibition studies showed that the a2C-AR is fine-tuned to respond to low-frequency stimulation (i.e., low norepinephrine concentrations), whereas the o a-AR is geared to respond to high-frequency stimulation (i.e., high norepinephrine concentrations as would be elicited by sympathetic activation). 

The catecholaminergic and serotonergic neurons in the mesencephalon are excellent models to study the enhancer regulation since their physiological function is to supply the brain continuously with the proper amounts of monoamines that influence - activate or inhibit - billions of neurons. The significant enhancement of the nerve-stimulation-induced release of [3H]-norepinephrine, [3H]-dopamine, and [3H]-serotonin from the isolated brain stem of the rat in the presence of PEA (Fig. 3.1) or tryptamine (Fig. 3.2) is shown to illustrate the response of enhancer-sensitive neurons to endogenous enhancer substances. 

In a study the effect of uptake inhibitors (desmethylimipramine, fluoxetine), a selective MAO-A inhibitor (clorgyline), a selective MAO-B inhibitor (laz-abemide), and dopamine receptor stimulants (pergolide, bromocriptine) - in comparison to the effect of (-)-BPAP - was measured on electrical-stimulation-induced release of labeled transmitters from the isolated brain stem of rats following labeling with [3H]-norepinephrine or [3H]-dopamine or [3H]-ser-otonin by preincubation in transmitter stores. The study confirmed the selectivity of the enhancer effect of (-)-BPAP (Miklya and Knoll 2003). 

Tatsumi, M. et al.. Mechanism of palytoxin-induced [3H]norepinephrine release from a rat pheochro-mocytoma cell line. Mol. Pharmacol. 25, 379, 1984. 

In contrast, following a treatment regimen of 20 mg/kg MDMA, there were no significant differences in the density of [3H]mazindol-labeled norepinephrine (NE) uptake sites (fmol/mg protein) in the frontal cerebral cortex between saline-treated (159 17) and MDMA-treated (152 5) animals. With respect to the dose of MDMA, serotonin levels appeared to be more readily decreased (45 percent reduction at 5 mg/kg), while comparable reductions in 5-HlAA levels and serotonin uptake sites were noted only at 10 or 20 mg/kg MDMA. This apparent discrepancy among the three serotonergic markers measured in the present study may relate to effects of lower doses of MDMA on synthetic enzyme activity (i.e., TPH), whereas the effects of higher doses of MDMA in reducing all three markers may relate in part to effects on TPH activity and in part to destruction of serotonin neurons as evidenced by decreases in serotonin uptake sites. 

Dopamine /3-hydroxylase (D/3H) is a copper-containing glycoprotein that hydroxylates dopamine at the benzylic position to norepinephrine.84 During the attempted crystallization of the bis(hydroxide)-bridged dicopper(II) dimer, a side product was subsequently isolated (complex (63)), revealing intramolecular hydroxylation at a formally benzylic position of the tris(imidazo-lyl)phosphine ligand.85 The copper(II) center has an axially compressed TBP structure. 

Katz, R. 1., and Kopin, 1. J. (1969) Effect of D-LSD and related compounds on release of norepinephrine-3H and serotonin-3H evoked from brain slices by electrical stimulation. Pharmacol. Res. Commun., 1 54-62. 

Ronde P, Nichols RA (1998) High calcium permeability of serotonin 5-HT3 receptors on presynaptic nerve terminals from rat striatum. J Neurochem 70 1094-1103 Rosenstein RE, Chuluyan HE, Cardinali DP (1990) Presynaptic effects of gamma-aminobutyric acid on norepinephrine release and uptake in rat pineal gland. J Neural Transm 82 131—40 Rousseau SJ, Jones IW, Pullar IA, Wonnacott S (2005) Presynaptic [alpha]7 and non-[alpha]7 nicotinic acetylcholine receptors modulate [3H]d-aspartate release from rat frontal cortex in vitro. Neuropharmacology 49 59... 

Fig. 15. Dopamine transporter binding (as revealed by [3H] mazindol in the presence of desmethylimipramine, to block binding to the norepinephrine transporter) in the post-mortem striatum of a human cocaine user and normal control subject. A reduction of the dopamine transporter binding sites was found in association with cocaine use in this population (taken from Hurd and Herkenham, 1993).

Pharmacology. In order to assess the importance of conformational preferences in the action of amphetamine at the adrenergic nerve endings, the effect of the amphetamine and methamphetamine analogs (NH-X,-NH-N, NM-X and NM-N) on the uptake and release of JH-norepinephrine (NE) and H-dopamine (DA) in chopped tissues from various regions of rat brain was examined. NH-X and NM-X were nearly as potent as amphetamine in the inhibition of uptake of 3H-NE into chopped cortex... 

Dual acting norepinephrine reuptake inhibitors and 5-HT2A receptor antagonists ii Synthesis and activity of novei spiro[cyciohexane-1,3 -[3H]indoi]-2 (1 H)-ones... 

---