High-affinity [3H]desipramine binding in the peripheral and central nervous system: A specific site associated with the neuronal uptake of noradrenaline

Raisman, Rita; Sette, Mario; Pimoule, C.; Briley, Mike; Langer, Salomón Z.

doi:10.1016/0014-2999(82)90036-x

Cited by 113 publications

(29 citation statements)

References 10 publications

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“…Membrane preparations for binding assays were prepared as described previously, with some minor modifications [26]. Rat hearts were excised and the ventricles were divided into four parts: the anterior, lateral, inferior, and the septal walls.…”

Section: Animalsmentioning

confidence: 99%

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Norepinephrine transporter density as a causative factor in alterations in MIBG myocardial uptake in NIDDM model rats

et al. 2002

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Cardiac scintigraphic studies with iodine-123 labeled metaiodobenzylguanidine ([(123)I]MIBG) have demonstrated global and regionally pronounced decreases in myocardial accumulation of radioactivity in diabetes. The aim of this study was to investigate the cause of the regional differential decrease in accumulation. To this end, we investigated the global and regional myocardial distribution of [(125)I]MIBG in GK/Crj (GK) rats [a model of non-insulin-dependent diabetes mellitus (NIDDM)] and assessed the responsibility of regional myocardial blood flow, myocardial and plasma norepinephrine (NE) content, and norepinephrine transporter (NET) function for the regional variations in [(125)I]MIBG accumulation. To investigate the responsibility of myocardial blood flow for the alterations in MIBG accumulation, dual-isotope autoradiographic studies with [(125)I]MIBG and technetium-99m hexakis-2-methoxy-2-isobutylisonitrile (MIBI), a tracer for the measurement of myocardial blood flow, were carried out in GK rats and control rats. The results in respect of the uptake of radioactivity into various myocardial regions were expressed as distribution absorption ratios [DAR = (radioactivity of tissue/g of tissue) x (body weight/total injected dose)]. In control rats, uptake of [(125)I]MIBG was significantly higher in the inferior wall than in the anterior wall (anterior wall, 6.35 +/- 0.90; inferior wall, 8.12 +/- 1.27: P < 0.001). On the other hand, in GK rats, uptake of [(125)I]MIBG was similar between the anterior wall and the inferior wall (anterior wall, 4.91 +/- 0.71; inferior wall, 4.81 +/- 0.69). Compared with control rats, uptake of [(125)I]MIBG in GK rats was decreased in both the anterior wall and the inferior wall. Uptake of (99m)Tc-MIBI was not significantly different between the anterior and inferior walls in control (anterior wall, 17.9 +/- 4.42; inferior wall, 18.1 +/- 4.52) and GK rats (anterior wall, 16.6 +/-8.03; inferior wall, 16.7 +/- 7.90), indicating that myocardial blood flow did not change regionally in either control or GK rats, and that the blood flow was not responsible for the differential decrease in MIBG accumulation in GK rats. Cardiac and plasma NE levels were measured using an HPLC-electrochemical detection system. The cardiac and plasma NE concentrations were not significantly different between control (anterior wall, 347 +/- 56 ng/g; inferior wall, 354 +/- 31 ng/g; plasma 9.38 +/- 2.10 ng/ml) and GK rats (anterior wall, 323 +/- 62 ng/g; inferior wall, 344 +/- 35 ng/g; plasma, 9.41 +/- 2.39 ng/ml). The density and affinity of NET were investigated by studying the binding of [(3)H]desipramine to cardiac membranes. The B(max) (fmol/mg protein) in the inferior wall was significantly higher than that in the anterior wall in the control rats (anterior wall, 364 +/- 28; inferior wall, 459 +/- 36: P < 0.05). On the other hand, there was no significant difference in the B(max) value between the anterior and inferior walls in GK rats (anterior wall, 263 +/- 42; inferior wall, 251 +/- 27). In conclusion,...

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Section: Animalsmentioning

confidence: 99%

“…Binding assays were performed as described previously with some modifications [26,28,29]. Briefly, [ 3 H]desipramine binding was determined by incubating aliquots of membrane suspension with [ 3 H]desipramine (0.25~30 nM) in a final volume of 250 µl for 30 min at 25°C.…”

Section: Animalsmentioning

confidence: 99%

Norepinephrine transporter density as a causative factor in alterations in MIBG myocardial uptake in NIDDM model rats

et al. 2002

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“…Various factors affecting the concentration of noradrenaline in the synaptic cleft may account for these differences between tissues, and the smooth muscle of the rat vas deferens has the densest innervation and probably the narrower synaptic cleft (10-30 nm) (Furness & Iwajama, 1971), as compared to other noradrenergically innervated tissues. A high affinity binding site for [3H]-desipramine, apparently associated with the neuronal noradrenaline uptake complex, is present in both peripheral and central tissues possessing noradrenergic innervation (Raisman et al, 1982) and it has been demonstrated that there is a 16 fold higher binding capacity for this ligand in the rat vas deferens compared to the rat cerebral cortex (1680 versus 101 fmol mg' protein), data that are in parallel with the endogenous noradrenaline content determined in both tissues (12756 versus 120 ng g' tissue) (Langer et al, 1984). Thus, the increase in noradrenaline concentration in the synaptic cleft following inhibition of neuronal noradrenaline uptake is likely to be greater in the rat vas deferens than in other tissues.…”

Section: Adaptation Of A-adrenoceptors In Rat Vas Deferens 681mentioning

confidence: 99%

Modulation of α₁‐adrenoceptors and functional consequences in the bisected rat vas deferens following chronic inhibition of neuronal noradrenaline uptake

Sallés

Badı́a

1993

British J Pharmacology

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reduction in density of a,-adrenoceptors was higher in the epididymal than the prostatic half. Desipramine reduced the B. only in the epididymal portion. 5 These results indicate that differential regulation of ax-adrenoceptors in either portion of the rat vas deferens could result from a greater degree of activation of these receptors in the epididymal half after chronic inhibition of neuronal noradrenaline uptake. The different functional consequences of the loss of al-adrenoceptors in each portion seems to be explained on the basis of a different relationship between the occupancy of the receptor and the response elicited.

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“…Uptake of exogenously added radiolabelled catecholamines has been demonstrated in peripheral and central neurones in vivo, in isolated peripheral tissues as well as brain slices and synaptosomal preparations (Glowinski, Kopin & Axelrod, 1965;Iversen, 1968Iversen, , 1971Snyder & Coyle, 1969;Langer, 1970;Koe, 1976;Reith, Sershen, Allen & Lajtha, 1983). Autoradiographic studies have demonstrated that the major site of noradrenaline uptake is on the sympathetic and central noradrenergic nerve fibres themselves (Lee & Snyder, 1981;Raisman, Sette, Pimoule, Briley & Langer, 1982;Rehavi, Skolnick, Brownstein & Paul, 1982); in peripheral tissue these uptake sites disappear after sympathectomy (Raisman et al 1982). Cocaine is well known to enhance the peripheral effects of post-ganglionic sympathetic stimulation (Trendelenburg, 1968;Iversen, 1968) and many of the profound behavioural effects of cocaine have been tentatively attributed to an enhancement of the actions of centrally released catecholamines (Kuczenski, 1983;Wise, 1984).…”

Section: Introductionmentioning

confidence: 99%

Inhibitory synaptic potentials recorded from mammalian neurones prolonged by blockade of noradrenaline uptake.

Surprenant¹,

Williams²

1987

The Journal of Physiology

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SUMMARY1. Intracellular recordings of membrane potential and membrane current were made from neurones of the rat nucleus locus coeruleus and the guinea-pig submucous plexus. These neurones exhibit inhibitory post-synaptic potentials (i.p.s.p.s) which result from noradrenaline acting on a2-adrenoceptors to cause an increase in potassium conductance. 3. Cocaine (10 AM) produced a maintained hyperpolarization (2-10 mV) or outward current (20-120 pA) in locus coeruleus neurones; in submucous plexus neurones cocaine increased the amplitude and duration of spontaneous i.p.s.p.s.4. Outward currents produced by superfusion with noradrenaline were increased by cocaine with maximum effects being observed at 10-30 /LM-cocaine. The maximum leftward shift in the relation between outward current or membrane hyperpolarization and noradrenaline concentration was 18-to 100-fold in locus coeruleus neurones and 4-fold in submucous plexus neurones. The concentrations of cocaine which caused a half-maximal increase in sensitivity to superfused noradrenaline were similar in both tissues, being 4 fIM in locus coeruleus and 2 fSM in submucous plexus.5. These results show that neuronal uptake of noradrenaline released from adrenergic nerves plays a significant role in determining the time course of synaptic potentials mediated by noradrenaline.

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High-affinity [3H]desipramine binding in the peripheral and central nervous system: A specific site associated with the neuronal uptake of noradrenaline

Cited by 113 publications

References 10 publications

Norepinephrine transporter density as a causative factor in alterations in MIBG myocardial uptake in NIDDM model rats

Norepinephrine transporter density as a causative factor in alterations in MIBG myocardial uptake in NIDDM model rats

Modulation of α₁‐adrenoceptors and functional consequences in the bisected rat vas deferens following chronic inhibition of neuronal noradrenaline uptake

Inhibitory synaptic potentials recorded from mammalian neurones prolonged by blockade of noradrenaline uptake.

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High-affinity [3H]desipramine binding in the peripheral and central nervous system: A specific site associated with the neuronal uptake of noradrenaline

Cited by 113 publications

References 10 publications

Norepinephrine transporter density as a causative factor in alterations in MIBG myocardial uptake in NIDDM model rats

Norepinephrine transporter density as a causative factor in alterations in MIBG myocardial uptake in NIDDM model rats

Modulation of α1‐adrenoceptors and functional consequences in the bisected rat vas deferens following chronic inhibition of neuronal noradrenaline uptake

Inhibitory synaptic potentials recorded from mammalian neurones prolonged by blockade of noradrenaline uptake.

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Modulation of α₁‐adrenoceptors and functional consequences in the bisected rat vas deferens following chronic inhibition of neuronal noradrenaline uptake