Mutagenesis of important amino acid reveals unconventional homologous internalization of β1-adrenergic receptor

Hossain, Murad; Rashid, Mamunur; Bhuiyan, Mohiuddin Ahmed; Nakamura, Takashi; Nagatomo, Takafumi

doi:10.1016/j.lfs.2009.06.015

Cited by 2 publications

(1 citation statement)

References 29 publications

(21 reference statements)

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“…Replacement of all of the Ser/Thr residues in the carboxyl-terminal tail and truncation of the domain containing these residues completely inhibited vasoactive intestinal polypeptide (VIP)-stimulated phosphorylation and receptor internalization ( Langlet et al, 2005 ). This GPCR internalization has been shown to be agonist-specific and G protein regulated kinase (GRK)-dependent ( Hossain et al, 2009 ). This type of feedback regulation is conventional, as it requires the activation of classic G proteins ( Kohout and Lefkowitz, 2003 ; Lodowski et al, 2003 ) as shown in Fig.…”

Section: Discussionmentioning

confidence: 99%

Internalization of Rat FSH and LH/CG Receptors by rec-eCG in CHO-K1 Cells

et al. 2017

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Equine chorionic gonadotropin (eCG) is a unique molecule that elicits the response characteristics of both follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in other species. Previous studies from this laboratory had demonstrated that recombinant eCG (rec-eCG) from Chinese hamster ovary (CHO-K1) cells exhibited both FSH- and LH-like activity in rat granulosa and Leydig cells. In this study, we analyzed receptor internalization through rec-eCGs, wild type eCG (eCGβ/α) and mutant eCG (eCGβ/αΔ56) with an N-linked oligosaccharide at Asn56 of the α-subunit. Both the rec-eCGs were obtained from CHO-K1 cells. The agonist activation of receptors was analyzed by measuring stimulation time and concentrations of rec-eCGs. Internalization values in the stably selected rat follicle-stimulating hormone receptor (rFSHR) and rat luteinizing/chorionic gonadotropin receptor (rLH/CGR) were highest at 50 min after stimulation with 10 ng of rec-eCGβ/α. The dose-dependent response was highest when 10 ng of rec-eCGβ/α was used. The deglycosylated eCGβ/αΔ56 mutant did not enhance the agonist-stimulated internalization. We concluded that the state of activation of rFSHR and rLH/CGR could be modulated through agonist-stimulated internalization. Our results suggested that the eLH/CGRs are mostly internalized within 60 min by agonist-stimulation by rec-eCG. We also suggested that the lack of responsiveness of the deglycosylated eCGβ/ αΔ56 was likely because the site of glycosylation played a pivotal role in agonist-stimulated internalization in cells expressing rFSHR and rLH/CGR.

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Section: Discussionmentioning

confidence: 99%

Internalization of Rat FSH and LH/CG Receptors by rec-eCG in CHO-K1 Cells

et al. 2017

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Prevention of cardiac events caused by surgical stress in aged rats: simultaneously activating β₂-adrenoceptor and inhibiting β₁-adrenoceptor

Sun¹,

Wang²,

Zhang³

et al. 2014

Stress

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Increased plasma catecholamine levels are associated with a high risk of perioperative cardiac events in aged individuals undergoing non-cardiac surgical interventions. Given the different effects of β1-adrenoreceptor (β1AR) and β2-adrenoreceptor (β2AR) stimulation by catecholamine in cardiomyocytes, this study evaluated whether simultaneous inhibition of β1AR and activation of β2AR is better than separate application in reducing the risk of perioperative cardiac events in aged rats undergoing non-cardiac surgery. Male aged Sprague-Dawley (SD) rats were divided into five groups. Normal group received no treatment. Surgery group received an abdominal surgery with hypoxia. β1- group, β2+ group, β2+ group and β1+β2+ group received surgery and hypoxia with metoprolol (100 mg/kg·d), fenoterol (250 μg/kg·d) or both, respectively. The drugs were given three days before surgery with treatment continued through post-surgical day 7. The results showed that simultaneous activation of β2AR with a β2AR agonist and inhibition of β1AR with a selective β1AR blocker normalized myocardial oxygen consumption, decreased myocardial damage, augmented cardiomyocyte survival, improved cardiac function, reduced the incidence of arrhythmia, thus decreasing the occurrence of cardiac events in perioperative aged rats undergoing non-cardiac surgery. The results demonstrated that combined use of β2AR agonist and β1AR blocker achieved better general effects than use of either one alone. Our results provide a new insight into preventing perioperative cardiac events for elderly patients undergoing surgical stress.

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Mutagenesis of important amino acid reveals unconventional homologous internalization of β1-adrenergic receptor

Cited by 2 publications

References 29 publications

Internalization of Rat FSH and LH/CG Receptors by rec-eCG in CHO-K1 Cells

Internalization of Rat FSH and LH/CG Receptors by rec-eCG in CHO-K1 Cells

Prevention of cardiac events caused by surgical stress in aged rats: simultaneously activating β₂-adrenoceptor and inhibiting β₁-adrenoceptor

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Mutagenesis of important amino acid reveals unconventional homologous internalization of β1-adrenergic receptor

Cited by 2 publications

References 29 publications

Internalization of Rat FSH and LH/CG Receptors by rec-eCG in CHO-K1 Cells

Internalization of Rat FSH and LH/CG Receptors by rec-eCG in CHO-K1 Cells

Prevention of cardiac events caused by surgical stress in aged rats: simultaneously activating β2-adrenoceptor and inhibiting β1-adrenoceptor

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Prevention of cardiac events caused by surgical stress in aged rats: simultaneously activating β₂-adrenoceptor and inhibiting β₁-adrenoceptor