Loss of response on repetitive drug exposure (i.e., tachyphylaxis) is a particular problem for the vasoconstrictor effects of medications containing oxymetazoline (OXY), an α1-adrenoceptor (AR) agonist of the imidazoline class. One cause of tachyphylaxis is receptor desensitization, usually accompanied by phosphorylation and internalization. It is well established that α1A-ARs are less phosphorylated, desensitized, and internalized on exposure to the phenethylamines norepinephrine (NE), epinephrine, or phenylephrine (PE) than are the α1B and α1D subtypes. However, here we show in human embryonic kidney-293 cells that the low-efficacy agonist OXY induces G protein-coupled receptor kinase 2-dependent α1A-AR phosphorylation, followed by rapid desensitization and internalization (∼40% internalization after 5 minutes of stimulation), whereas phosphorylation of α1A-ARs exposed to NE depends to a large extent on protein kinase C activity and is not followed by desensitization, and the receptors undergo delayed internalization (∼35% after 60 minutes of stimulation). Native α1A-ARs from rat tail artery and vas deferens are also desensitized by OXY, but not by NE or PE, indicating that this property of OXY is not limited to recombinant r...Continue Reading
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Differential distribution of functional alph}1-adrenergic receptor subtypes along the rat tail artery
Agonist-selective mechanisms of mu-opioid receptor desensitization in human embryonic kidney 293 cells
Internalization and distribution of three alpha1-adrenoceptor subtypes in HEK293A cells before and after agonist stimulation
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Selective engagement of G protein coupled receptor kinases (GRKs) encodes distinct functions of biased ligands.
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Roles of the α1A-adrenergic receptor carboxyl tail in protein kinase C-induced phosphorylation and desensitization
Agonist-selective patterns of µ-opioid receptor phosphorylation revealed by phosphosite-specific antibodies.
Long-term α1A-adrenergic receptor stimulation improves synaptic plasticity, cognitive function, mood, and longevity
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Potential Role of Catecholamine Response to Acute Hypoxia in the Modification of the Effects of Radioprotectors
Neurovascular mechanisms underlying augmented cold-induced reflex cutaneous vasoconstriction in human hypertension
S1P1 receptor phosphorylation, internalization, and interaction with Rab proteins: effects of sphingosine 1-phosphate, FTY720-P, phorbol esters, and paroxetine
Photopic light-mediated down-regulation of local α1A -adrenergic signaling protects blood-retina barrier in experimental autoimmune uveoretinitis
Reversal of Vasodilatory Shock: Current Perspectives on Conventional, Rescue, and Emerging Vasoactive Agents for the Treatment of Shock
Impaired increases in skin sympathetic nerve activity contribute to age-related decrements in reflex cutaneous vasoconstriction
Coupling to Gq Signaling Is Required for Cardioprotection by an Alpha-1A-Adrenergic Receptor Agonist
Angiotensin II and Vasopressin for Vasodilatory Shock: A Critical Appraisal of Catecholamine-Sparing Strategies.
Heterozygous disruption of activin receptor-like kinase 1 is associated with increased arterial pressure in mice
Current Developments on the Role of α1-Adrenergic Receptors in Cognition, Cardioprotection, and Metabolism.
Adrenergic Receptors: Trafficking
Adrenergic receptor trafficking is an active physiological process where adrenergic receptors are relocated from one region of the cell to another or from one type of cell to another. Discover the latest research on adrenergic receptor trafficking here.