Imidazoline receptor proteins are regulated in platelet-precursor MEG-01 cells by agonists and antagonists

Ivanov, Tina R.; Feng, Yang Zheng; Wang, H.; Regunathan, S.; Reis, Donald J.; Chikkala, Deepak; Gupta, Priyanka; Jones, Julia C.; Piletz, John E.

doi:10.1016/s0022-3956(98)00006-5

Cited by 21 publications

(27 citation statements)

References 33 publications

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“…It is interesting to note that atrial 85-kDa but not the 29-kDa imidazoline receptor proteins vary in parallel to values of B max for I 1 -sites determined by 125 I-PIC binding. This correlation leads us to propose that the 85-kDa protein may represent I 1 -receptors in the heart, as has been suggested by Ivanov et al (1998). Furthermore, the positive correlation between changes in the two receptor proteins implies that they may arise from the same gene.…”

Section: Cardiac Imidazoline I 1 Receptors In Shr 449supporting

confidence: 54%

“…However, previous studies indicate that imidazoline receptors and ␣ 2 -adrenoceptors are subject to pathophysiological and pharmacological regulation (Yakubu et al, 1990;Ernsberger et al, 1991;Zhu et al, 1997;Ivanov et al, 1998). Therefore, the aim of the present studies was to test regulation of cardiac I 1 -receptors versus ␣ 2 -adrenoceptors, by showing that I 1 -receptors, but not ␣ 2 -adrenoceptors are regulated in hypertension and in response to exposure to agonist.…”

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confidence: 85%

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Imidazoline Receptors but Not α₂-Adrenoceptors Are Regulated in Spontaneously Hypertensive Rat Heart by Chronic Moxonidine Treatment

El-Ayoubi¹,

Ménaouar²,

Gutkowska³

et al. 2004

J Pharmacol Exp Ther

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We have recently identified imidazoline I 1 -receptors in the heart. In the present study, we tested regulation of cardiac I 1 -receptors versus ␣ 2 -adrenoceptors in response to hypertension and to chronic exposure to agonist. Spontaneously hypertensive rats (SHR, 12-14 weeks old) received moxonidine (10, 60, and 120 g/kg/h s.c.) for 1 and 4 weeks. Autoradiographic binding of 125 I-paraiodoclonidine (0.5 nM, 1 h, 22°C) and inhibition of binding with epinephrine (10 Ϫ10 -10 Ϫ5 M) demonstrated the presence of ␣ 2 -adrenoceptors in heart atria and ventricles. Immunoblotting and reverse transcription-polymerase chain reaction identified ␣ 2A -, ␣ 2B -, and ␣ 2C -adrenoceptor proteins and mRNA, respectively. However, compared with normotensive controls, cardiac ␣ 2 -adrenoceptor kinetic parameters, receptor proteins, and mRNAs were not altered in SHR with or without moxonidine treatment. In contrast, autoradiography showed that up-regulated atrial I 1 -receptors in SHR are dose-dependently normalized by 1 week, with no additional effect after 4 weeks of treatment. Moxonidine (120 g/kg/h) decreased B max in right (40.0 Ϯ 2.9 -7.0 Ϯ 0.6 fmol/unit area; p Ͻ 0.01) and left (27.7 Ϯ 2.8 -7.1 Ϯ 0.4 fmol/unit area; p Ͻ 0.01) atria, and decreased the 85-and 29-kDa imidazoline receptor protein bands, in right atria, to 51.8 Ϯ 3.0% (p Ͻ 0.01) and 82.7 Ϯ 5.2% (p Ͻ 0.03) of vehicle-treated SHR, respectively. Moxonidine-associated percentage of decrease in B max only correlated with the 85-kDa protein (R 2 ϭ 0.57; p Ͻ 0.006), suggesting that this protein may represent I 1 -receptors. The weak but significant correlation between the two imidazoline receptor proteins (R 2 ϭ 0.28; p Ͻ 0.03) implies that they arise from the same gene. In conclusion, the heart possesses I 1 -receptors and ␣ 2 -adrenoceptors, but only I 1 -receptors are responsive to hypertension and to chronic in vivo treatment with a selective I 1 -receptor agonist.

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Section: Cardiac Imidazoline I 1 Receptors In Shr 449supporting

confidence: 54%

mentioning

confidence: 85%

Imidazoline Receptors but Not α₂-Adrenoceptors Are Regulated in Spontaneously Hypertensive Rat Heart by Chronic Moxonidine Treatment

El-Ayoubi¹,

Ménaouar²,

Gutkowska³

et al. 2004

J Pharmacol Exp Ther

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“…Western blots revealed an increase in IRBP‐immunodensity in a 33 kD band in 21 untreated depressed patients as compared to 17 healthy control subjects 33. The 33 kD band has previously been correlated with I I binding sites on platelets 30. After 6 weeks of bupropion treatment, IRBP‐immunodensity was down‐regulated in the total group, but the effect was much more pronounced in the subset of treatment responders ( P = 0.005).…”

Section: Platelet Studies Of I‐sites In Depressionmentioning

confidence: 84%

“…Presynaptic α 2 AR modulate the release of norepinephrine (NE), serotonin (5HT), and other neurotransmitters and are therefore potential targets for antidepressant and anxiolytic drug development. Human platelets also possess I 1 and I 2 subtypes of imidazoline binding sites3,35 as well as immuno‐related 33 kD and 45 kD proteins 30,31. Our group published the first studies of I 1 binding sites in platelets from depressed patients and compared their binding density and affinity to that of matched healthy control subjects 36–38.…”

Section: Platelet Studies Of I‐sites In Depressionmentioning

confidence: 99%

Relevance of Imidazoline Receptors and Agmatine to Psychiatry: A Decade of Progress

Halaris

2003

Annals of the New York Academy of Sciences

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The cardiovascular relevance of imidazoline receptors (IR) has received tremendous attention since their discovery in 1984. However, evidence also has accumulated for the relevance of IR and an endogenous ligand, agmatine, to psychiatric disease. Emphasis has been placed on altered levels of the I(1)-imidazoline site on human platelets and in human postmortem brain tissue from depressed patients. Attempts at exploring the molecular nature of the I(1) protein have led to the cloning of a protein, IRAS. Based on transfection studies, IRAS seems to be involved in neuronal plasticity events. The I(2) site also appears linked to psychiatric research since some of these sites are localized to a specific domain on monoamine oxidases. Different peptides have been identified by means of an imidazoline-receptor-binding-protein (IRBP) antiserum, and these peptides, some of which appear to be fragments derived from IRAS, undergo changes in platelets and brain commensurate with altered mood states of the subject, notably depressive symptomatology. The search for an endogenous ligand for imidazoline receptor(s) also has led to agmatine, a decarboxylated derivative of arginine. Research on agmatine has mushroomed over the past several years and its measurement in the blood and brain has opened new research opportunities. This novel neurotransmitter interacts with a variety of receptors and has been implicated in mediation of stress responses, analgesia, drug addiction and withdrawal, convulsions, and neuroprotection. Given that IR and agmatine appear involved in a multitude of neurophysiologic and pathologic functions, the potential for new drug development is intriguing.

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“…Agmatine has been shown to exert several actions that are related to its ability to inhibit NMDA receptors [4,19,30]. The protective effects of agmatine on excitotoxic injury in vitro and ischemic injury in vivo are well documented [4,6,11,12,32,33]. While the centrally administered agmatine potentiates morphine analgesia, peripheral agmatine reduces morphine tolerance and withdrawal symptoms [2,13,14,31].…”

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confidence: 99%

Agmatine reduces extracellular glutamate during pentylenetetrazole-induced seizures in rat brain: A potential mechanism for the anticonvulsive effects

Feng

LeBlanc

Regunathan

2005

Neuroscience Letters

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Glutamate has been implicated in the initiation and spread of seizure activity. Agmatine, an endogenous neuromodulator, is an antagonist of NMDA receptors and has anticonvulsive effects. Whether agmatine regulate glutamate release, as measured by in vivo microdialysis, is not known. In this study, we used pentylenetetrazole (PTZ)-induced seizure model to determine the effect of agmatine on extracellular glutamate in rat brain. We also determined the time course and the amount of agmatine that reached brain after peripheral injection. After i.p. injection of agmatine (50 mg/kg), increase of agmatine in rat cortex and hippocampus was observed in 15 min with levels returning to baseline in one hour. Rats, naïve and implanted with microdialysis cannula into the cortex, were administered PTZ (60 mg/kg, i.p.) with prior injection of agmatine (100 mg/kg, i.p.) or saline. Seizure grades were recorded and microdialysis samples were collected every 15 min for 75 min. Agmatine pre-treatment significantly reduced the seizure grade and increased the onset time. The levels of extracellular glutamate in frontal cortex rose two-to three-fold after PTZ injection and agmatine significantly inhibited this increase. In conclusion, the present data suggest that the anticonvulsant activity of agmatine, in part, could be related to the inhibition glutamate release. KeywordsAgmatine; Pentylenetetrazole; Glutamate; Microdialysis; Seizures Agmatine is an amine, synthesized by decarboxylation of Larginine by arginine decarboxylase (ADC) [16,23]. Agmatine is widely distributed in mammalian tissue [5,22] including brain where it is unevenly distributed in various regions and enriched in subcortical regions [21]. Although the physiological functions of agmatine in the brain is still not clear, accumulating evidence indicates several pharmacological actions of agmatine. The facts that agmatine binds to NMDA receptors [25], selectively blocks NMDA receptor channels in neurons [19,30] and localized in excitatory synapses in hippocampus [24] suggest that agmatine could regulate glutamatergic neurotransmission. Moreover, agmatine inhibits the release of vasopressin in neurohypophysis [29] and norepinephrine from perivascular nerve terminals [9], suggesting a pre-synaptic action regulating the release of neuro-transmitters. Functional effects such as protection against ischemic neuronal injury [4,6,8,12,19,32,33] In initial experiments, we administered agmatine to rats (50 mg/kg, i.p.) and measured the levels of agmatine in cortex and hippocampus at different time points. Rat brain regions were dissected out and processed for HPLC measurement of agmatine as described earlier [5]. A typical HPLC chromatogram of agmatine is shown in Fig. 1 for cortex samples prepared from 15 min, 1 and 2 h after agmatine injection. Agmatine values from cortex and hippocampus at all time points after agmatine injection are shown in Table 1. The levels of agmatine in cortex and hippocampus increased to two-to four-fold at 15 min, started to decrease at 30 min ...

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Imidazoline receptor proteins are regulated in platelet-precursor MEG-01 cells by agonists and antagonists

Cited by 21 publications

References 33 publications

Imidazoline Receptors but Not α₂-Adrenoceptors Are Regulated in Spontaneously Hypertensive Rat Heart by Chronic Moxonidine Treatment

Imidazoline Receptors but Not α₂-Adrenoceptors Are Regulated in Spontaneously Hypertensive Rat Heart by Chronic Moxonidine Treatment

Relevance of Imidazoline Receptors and Agmatine to Psychiatry: A Decade of Progress

Agmatine reduces extracellular glutamate during pentylenetetrazole-induced seizures in rat brain: A potential mechanism for the anticonvulsive effects

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Imidazoline receptor proteins are regulated in platelet-precursor MEG-01 cells by agonists and antagonists

Cited by 21 publications

References 33 publications

Imidazoline Receptors but Not α2-Adrenoceptors Are Regulated in Spontaneously Hypertensive Rat Heart by Chronic Moxonidine Treatment

Imidazoline Receptors but Not α2-Adrenoceptors Are Regulated in Spontaneously Hypertensive Rat Heart by Chronic Moxonidine Treatment

Relevance of Imidazoline Receptors and Agmatine to Psychiatry: A Decade of Progress

Agmatine reduces extracellular glutamate during pentylenetetrazole-induced seizures in rat brain: A potential mechanism for the anticonvulsive effects

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Product

Resources

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Imidazoline Receptors but Not α₂-Adrenoceptors Are Regulated in Spontaneously Hypertensive Rat Heart by Chronic Moxonidine Treatment

Imidazoline Receptors but Not α₂-Adrenoceptors Are Regulated in Spontaneously Hypertensive Rat Heart by Chronic Moxonidine Treatment