High‐affinity uptake of noradrenaline in postsynaptic neurones

Al-Damluji, Saad; Krsmanović, Lazar Z.; Catt, K. J.

doi:10.1111/j.1476-5381.1993.tb13570.x

Cited by 21 publications

(36 citation statements)

References 52 publications

(67 reference statements)

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“…Our results were not consistent with the findings of Al-Damluji et al [15]. The reason for this discrepancy is not known, but Al-Damluji et al [15] …”

Section: Discussioncontrasting

confidence: 57%

“…Moreover, we demonstrated that NA increased [Ca2+]i and depolarized membrane potentials via f3-adrenergic receptors in GT1-7 cells. Al-Damluji et al [15] found that the a1-adrenoceptor ligand [3HFprazosin bound with high affinity and was displaced by unlabelled prazosin in GT1-1 cells. Our results were not consistent with the findings of Al-Damluji et al [15].…”

Section: Discussionmentioning

confidence: 99%

“…Al-Damluji et al [15] found that the a1-adrenoceptor ligand [3HFprazosin bound with high affinity and was displaced by unlabelled prazosin in GT1-1 cells. Our results were not consistent with the findings of Al-Damluji et al [15]. The reason for this discrepancy is not known, but Al-Damluji et al [15] …”

Section: Discussionmentioning

confidence: 99%

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Effects of Noradrenaline on GnRH-Secreting Immortalized Hypothalamic (GT1-7) Neurons.

et al. 1997

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Abstract. Noradrenaline (NA) is one of the most important neurotransmitters involved in the regulation of gonadotropin-releasing hormone (GnRH) secretion. In this study, the effects of NA on GnRH secretion, intracellular Ca2+ concentrations ([Ca2+]i), and membrane potentials were investigated in immortalized hypothalamic neurons (GT1-7) to determine the direct effects of NA on GnRH cells. Cells were perfused in a plastic minicolumn, and GnRH concentrations of the effluents were measured. NA increased the release of GnRH in a dose-dependent manner. Cells were loaded with 4 pM Fura 2-AM, and the ratio of the intensities of fluorescent emission at 510 nm with excitation at 340 and 380 nm was calculated at 100-ms intervals. NA increased the [Ca2+]i responses of single GnRH cells dosedependently.The NA-induced [Ca2+]i increase was attenuated in the absence of extracellular calcium and was blocked by the 13-adrenergic antagonist propranolol, but not by the a-adrenergic antagonist phentolamine. The cell membrane potential was recorded with a whole-cell patch clamp amplifier with glass-electrodes.NA induced membrane depolarization under current-clamp conditions. The depolarization was also inhibited by propranolol, but not by phentolamine.The results show that NA directly affects the membrane potential of GT1-7 cells via fJ-adrenergic receptors and induces Ca2+ mobilization; these effects stimulate GnRH secretion.

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“…Our results were not consistent with the findings of Al-Damluji et al [15]. The reason for this discrepancy is not known, but Al-Damluji et al [15] …”

Section: Discussioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

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Effects of Noradrenaline on GnRH-Secreting Immortalized Hypothalamic (GT1-7) Neurons.

et al. 1997

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“…AC-induced cAMP production occurs in response to dopamine and norepinephrine (Jarry et al, 1990;Martínez de la Escalera 1992b,c;Al-Damluji et al, 1993). In general, cAMP can act indirectly, by modulating various ionic currents in a protein kinase A-dependent manner, or directly, via modulation of cyclic nucleotide-gated (CNG) channels, which have been identified in GT1 neurons (Vitalis et al, 2000).…”

Section: Abstract: Gt1 Neurons; Mathematical Modeling; Voltagegated mentioning

confidence: 99%

Modeling of Membrane Excitability in Gonadotropin-Releasing Hormone-Secreting Hypothalamic Neurons Regulated by Ca²⁺-Mobilizing and Adenylyl Cyclase-Coupled Receptors

et al. 2000

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Gonadotropin-releasing hormone (GnRH) secretion from native and immortalized hypothalamic neurons is regulated by endogenous Ca 2ϩ -mobilizing and adenylyl cyclase (AC)-coupled receptors. Activation of both receptor types leads to an increase in action potential firing frequency and a rise in the intracellular pool mimics the receptor-induced activation of I SOC and I SK , leading to an increase in the firing frequency and Ca 2ϩ influx after a transient cessation of electrical activity. However, increasing the activity of I d simulates the experimental response to forskolin-induced activation of AC. Analysis of the behaviors of I SOC , I d , and I SK in the model reveals the complexity in the interplay of these currents that is necessary to fully account for the experimental results.

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“…While studying the functional properties of a1-adrenoceptors in the hypothalamus, we observed a high-affinity uptake process for amines in peptidergic neurones (Al-Damluji & Krsmanovic, 1992;Al-Damluji et al, 1993). In primary hypothalamic cell cultures and in a hypothalamic neuronal cell line, [3H]-prazosin bound with high affinity and was displaced by unlabelled prazosin in concentrations of 10-10 to 10-7 M. However, at concentrations of unlabelled prazosin greater than 10-7 M, there was a paradoxical increase in apparent [3H]-prazosin binding, which could be abolished by desipramine; in the presence of desipramine, unlabelled prazosin displaced [3H]-prazosin as before, but no increase in accumulation was seen above 10-7 M. The paradoxical increase of [3H]-prazosin binding was not observed in membrane preparations of hypothalamic neurones.…”

Section: Introductionmentioning

confidence: 96%

Functional properties of the uptake of amines in immortalised peptidergic neurones (transport‐P)

Al-Damluji

Kopin

1996

British J Pharmacology

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1Most neurotransmitters are inactivated by uptake into presynaptic nerve terminals and into glial cells. We recently provided evidence for uptake of amines in postsynaptic neurones. Uptake was evident at nanomolar concentrations of prazosin, but at concentrations of unlabelled prazosin greater than 10-M, there was a further activation of uptake, manifested by a paradoxical increase in accumulation of the radioligand. We have now studied further characteristics of amine uptake in immortalised gonadotrophin-releasing hormone (GnRH) neurones. Control cells included SK-N-SH neuroblastoma cells (which possess presynaptic type amine transporters) and non-neuronal (COS-7) cells. 2 [3H]-prazosin bound to intact GnRH cells and was displaced by unlabelled prazosin in concentrations of 10-to 10-' M. However, at higher concentrations of unlabelled prazosin, there was an increase in apparent [3H]-prazosin binding, as we had previously described. This paradoxical increase in accumulation of the radioligand was abolished by desipramine. 3 Desipramine had no effect on the association of prazosin with COS-7 cells. There was no paradoxical increase in accumulation of [3H]-prazosin in COS-7 cells, indicating that this effect requires the presence of a desipramine-blockable uptake process. 4 The increase in binding of the radioligand that was observed in the GnRH cells is not a general property of neuronal transporters; in SK-N-SH cells, there was no increase in accumulation of (-)-[3H]-noradrenaline in the presence of concentrations of unlabelled (-)-noradrenaline greater than 10-7 M. 5 The uptake of prazosin and the increase in accumulation of [3H]-prazosin were abolished in the cold, indicating that this is an active, energy-requiring process. 6 Desipramine-sensitive uptake of prazosin was demonstrable in the GnRH cells in the absence of sodium. Further, the Na+/K+-ATPase inhibitor, vanadate, abolished noradrenaline uptake in SK-N-SH cells but had no effect on prazosin uptake in GnRH cells. Thus, the uptake of prazosin does not derive its energy from the sodium pump.7 Prazosin uptake was inhibited by the V-ATPase inhibitor bafilomycin Al, the H+/Na+ ionophore, monensin and the organic base, chloroquine, indicating that uptake derives its energy from a proton pump. In contrast to other proton-dependent amine transporters, the uptake of prazosin was unaffected by reserpine. 8 Increasing extracellular pH did not increase the uptake of prazosin into GnRH cells, indicating that it is unlikely to be due to non-specific diffusion and concentration of a lysosomotropic drug into intracellular acidic particles. 9 The uptake of prazosin was unaffected by steroid hormones.10 In COS-7 cells transfected with ocl-adrenoceptor cDNA, [3H]-prazosin was displaced by unlabelled prazosin without causing an increase in binding of the radioligand. This indicated that the increase in accumulation of the radioligand is unlikely to be due simply to some function of a,-adrenoceptors.11 Thus, peptidergic neurones possess an uptake process with properties ...

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High‐affinity uptake of noradrenaline in postsynaptic neurones

Cited by 21 publications

References 52 publications

Effects of Noradrenaline on GnRH-Secreting Immortalized Hypothalamic (GT1-7) Neurons.

Effects of Noradrenaline on GnRH-Secreting Immortalized Hypothalamic (GT1-7) Neurons.

Modeling of Membrane Excitability in Gonadotropin-Releasing Hormone-Secreting Hypothalamic Neurons Regulated by Ca²⁺-Mobilizing and Adenylyl Cyclase-Coupled Receptors

Functional properties of the uptake of amines in immortalised peptidergic neurones (transport‐P)

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High‐affinity uptake of noradrenaline in postsynaptic neurones

Cited by 21 publications

References 52 publications

Effects of Noradrenaline on GnRH-Secreting Immortalized Hypothalamic (GT1-7) Neurons.

Effects of Noradrenaline on GnRH-Secreting Immortalized Hypothalamic (GT1-7) Neurons.

Modeling of Membrane Excitability in Gonadotropin-Releasing Hormone-Secreting Hypothalamic Neurons Regulated by Ca2+-Mobilizing and Adenylyl Cyclase-Coupled Receptors

Functional properties of the uptake of amines in immortalised peptidergic neurones (transport‐P)

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Modeling of Membrane Excitability in Gonadotropin-Releasing Hormone-Secreting Hypothalamic Neurons Regulated by Ca²⁺-Mobilizing and Adenylyl Cyclase-Coupled Receptors