Release of amino acids by zinc in the hippocampus

Takeda, Atsüshi; Minami, Akira; Seki, Yumiko; Nakajima, Satoko; Oku, Naoto

doi:10.1016/j.brainresbull.2004.03.003

Cited by 7 publications

(5 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Zn 2+ by itself caused a concentration‐dependent accumulation of cAMP and acted as a practically full agonist of MC 4 R with an EC 50 value of 1.1 μM. In the brain, free (rapidly exchangeable) zinc is mostly sequestered in the pre‐synaptic vesicles of glutamatergic nerve terminals, and upon stimulation, these zinc‐releasing neurons also release glutamate into the synaptic cleft (Minami, Takeda, Yamaide, and Oku, ; Takeda, Minami, Seki, Nakajima, and Oku, ). Upon stimulation, the free concentration of synaptically released zinc has been found to reach the 10–30 µM range on average in brain slices (Thompson, Whetsell, Maliwal, Fierke, and Frederickson, ; Li, Hough, Frederickson, and Sarvey, ; Li, Hough, Suh, Sarvey, and Frederickson, ; Ueno et al, ).…”

Section: Discussionmentioning

confidence: 99%

The constitutive activity of melanocortin‐4 receptors in cAMP pathway is allosterically modulated by zinc and copper ions

Link

Veikšina

Tahk

et al. 2019

Journal of Neurochemistry

View full text Add to dashboard Cite

Melanocortin‐4 receptors (MC4R) are unique among G‐protein‐coupled receptors (GPCRs) as they have endogenous ligands that can exhibit inverse agonistic properties in the case of elevated basal activity. It is known that the constitutive activity of GPCRs strongly affects the ligand‐dependent physiological responses, but little is known about these regulatory mechanisms. Since several metal ions have been shown to be important modulators of the signal transduction of GPCRs, we hypothesized that metal ions regulate the basal activity of MC4Rs. Implementation of a fluorescence anisotropy assay and novel redshifted fluorescent peptides enabled kinetic characterization of ligand binding to MC4R expressed on budded baculoviruses. We show that Ca2+ is required for high‐affinity ligand binding, but Zn2+ and Cu2+ in the presence of Ca2+ behave as negative allosteric modulators of ligand binding to MC4R. FRET‐based cAMP biosensor was used to measure the activation of MC4R stably expressed in CHO‐K1 cells. At low micromolar concentrations, Zn2+ caused MC4R‐dependent activation of the cAMP pathway, whereas Cu2+ reduced the activity of MC4R even below the basal level. These findings indicate that at physiologically relevant concentrations can Zn2+ and Cu2+ function as MC4R agonists or inverse agonists, respectively. This means that depending on the level of constitutive activity induced by Zn2+ ions, the pharmacological effect of orthosteric ligands of MC4R can be switched from a partial to an inverse agonist. Open Science Badges This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. More information about the Open Science badges can be found at https://cos.io/our-services/open-science-badges/.

show abstract

Section: Discussionmentioning

confidence: 99%

The constitutive activity of melanocortin‐4 receptors in cAMP pathway is allosterically modulated by zinc and copper ions

Link

Veikšina

Tahk

et al. 2019

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…The objective is to obtain an automatic and rapid simultaneous measurement of aspartate, serine, glutamate, glycine and histidine in a high number of small volume microdialysates of rat hippocampus during controls and under different experimental conditions. Serine has been included because of its involvement in synaptic transmission (Takeda et al, 2004) and epileptic seizures (Engstrom et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Analysis of neuroactive amino acids from microdialysate samples by fluorescence detection using a modification of the 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate method

Oreiro-García

Vázquez-Illanes

Sierra-Paredes

et al. 2005

Biomed. Chromatogr.

View full text Add to dashboard Cite

A sensitive and rapid reversed-phase high-performance liquid chromatographic method using pre-column derivatization with 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) and fluorescence detection is reported. By directly derivatizing microdialysate samples with AQC, an automatic and rapid simultaneous measurement of aspartate, serine, glutamate, glycine and histidine was developed. Excellent linearity (r2 > or = 0.998) was achieved for the standard mixture used for the validation experiments. Within-day and between-day precision was less than 6.2%, and the accuracy ranged from 95 to 105.2% in standards. This method is suitable for single run analysis of a high number of small volume microdialysate samples from rat hippocampus. Amino acids from microdialysate samples were quantified with RSD for reproducibility below 2%, and at approximately 0.1% for retention time.

show abstract

“…It has been reported that NR2A do not play a dominant role at early postnatal development in CNS including rat spinal cord (Portera-Cailliau et al, 1996;Stegenga and Kalb, 2001 , 2003) and that substance P causes the release of glutamate from the spinal cord of the neonatal rat (Maehara et al, 1995). Zn 2+ also increases the extracellular concentrations of excitatory amino acids such as aspartate and glutamate in the rat hippocampus (Takeda et al, 2004) and the substantia nigra (Dopico et al, 2004 (Schousboe, 2003;Watkins and Maier, 2003). Zn 2+ has been reported to inhibit the activity of glutamate transporters (Vandenberg et al, 1998;Mitrovic et al, 2001) that lower the extracellular glutamate level in the synaptic cleft.…”

Section: Characterization Of the Excitatory Effect Of Znmentioning

confidence: 99%

Zinc modulates primary afferent fiber-evoked responses of ventral roots in neonatal rat spinal cord in vitro

Otsuguro

Ohta

2006

Neuroscience

View full text Add to dashboard Cite

Release of amino acids by zinc in the hippocampus

Cited by 7 publications

References 24 publications

The constitutive activity of melanocortin‐4 receptors in cAMP pathway is allosterically modulated by zinc and copper ions

The constitutive activity of melanocortin‐4 receptors in cAMP pathway is allosterically modulated by zinc and copper ions

Analysis of neuroactive amino acids from microdialysate samples by fluorescence detection using a modification of the 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate method

Zinc modulates primary afferent fiber-evoked responses of ventral roots in neonatal rat spinal cord in vitro

Contact Info

Product

Resources

About