Alpha 2-Adrenergic Receptor Agonist Brimonidine Stimulates ERK1/2 and AKT Signaling via Transactivation of EGF Receptors in the Human MIO-M1 Muller Cell Line.
adrenergic receptors; AKT pathway; and Src-kinase; brimonidine; EGF receptor; ERK1/2; matrix metalloproteinases; Muller cell
PURPOSE: Alpha 2-adrenergic receptor (alpha2-ADR) agonists are used clinically for a range of indications including reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Animal experiments show that alpha2-ADR agonists attenuate the injury-induced Muller cell dedifferentiation by a mechanism that involves activation and regulation of extracellular signal-regulated kinase (ERK) 1/2 leading to transactivation of epidermal growth factor receptors (EGFRs). The purpose of this study was to study and corroborate the activation of this system in human cells. MATERIAL AND METHODS: The human Muller cell line MIO-M1 was treated with the alpha2A-ADR agonist brimonidine in combination with inhibitors for Src-kinase, EGFR-kinase, matrix metalloproteinase (MMP) as well as small interfering RNAs (siRNAs) for the EGFR. The cells were analyzed using immunocytochemistry, quantitative PCR and western blot techniques. RESULTS: Our results show that human MIO-M1 cells express alpha2A-ADRs and that stimulation of these receptors caused a robust increase of ERK1/2 and protein kinase B (PKB/AKT) (Thr-308) phosphorylation in
Harun-Or-Rashid Mohammad; Hallbook Finn
Current eye research
2019
2019-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1080/02713683.2018.1516783" target="_blank" rel="noreferrer noopener">10.1080/02713683.2018.1516783</a>
Higher Alpha-noradrenergic Receptors In Paraventricular Nucleus Of Obese Zucker Rats - Decline After Food-deprivation
adrenergic receptors; alpha-2-noradrenergic receptors; alpha-noradrenergic receptors; Behavioral Sciences; binding; brain-areas; circulating corticosterone; energy-expenditure; fa-fa; feeding behavior; feeding behavior; hypothalamic neuropeptide-y; hypothalamus; Neurosciences & Neurology; norepinephrine; obesity; paraventricular nucleus; Pharmacology & Pharmacy; zucker rats
Norepinephrine (NE), acting through alpha-2-noradrenergic receptors in the hypothalamic paraventricular nucleus (PVN), has been implicated in the control of feeding behavior and body weight gain. To determine whether this hypothalamic receptor system is disturbed in genetically obese rats, the binding of radioligands to alpha-2-noradrenergic, as well as to alpha-1-noradrenergic, receptors was examined in seven hypothalamic nuclei of obese Zucker rats relative to their lean littermates. Receptor binding procedures, using the alpha-2-noradrenergic agonist [H-3]p-aminoclonidine ([H-3]PAC) and the alpha-1-noradrenergic antagonist [H-3]prazosin, demonstrated that the obese rats, compared to the lean rats, had significantly greater alpha-2-noradrenergic and alpha-1-noradrenergic receptor binding, specifically in the PVN as opposed to other hypothalamic areas examined. Moreover, the obese rats, compared to the lean rats, exhibited greater responsiveness to the effects of food deprivation (48 h), which caused a significant decline in radioligand binding to both alpha-2 and alpha-1 receptors, specifically in the PVN. A decrease in alpha-2-receptor binding after deprivation in the obese rats was also seen in two basal hypothalamic areas, namely, the supraoptic nucleus and arcuate nucleus-median eminence. The possibility exists that these disturbances in hypothalamic alpha-receptors may be involved in the development and/or maintenance of the genetic obesity.
Jhanwaruniyal M; Awad I R; Gearhart G M; Finkelstein J A; Leibowitz S F
Pharmacology Biochemistry and Behavior
1991
1991-12
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1016/0091-3057(91)90097-l" target="_blank" rel="noreferrer noopener">10.1016/0091-3057(91)90097-l</a>