Regulation of β-Adrenergic receptor responsiveness modulation of receptor gene expression

Danner, Stefan; Lohse, Martin J.

doi:10.1007/bfb0032325

Cited by 10 publications

(4 citation statements)

References 183 publications

(215 reference statements)

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“…In contrast, hypoglycemic events associated with glucose levels of >2.75 mmol/l did not appear to result in β 2 -adrenoceptor downregulation. In vitro and in vivo results clearly demonstrate that downregulation is one of the mechanisms involved in receptor desensitization [25]. In agreement with our findings, after a 3-hour nocturnal hypoglycemia of <3 mmol/l, a significant reduction in β-adrenergic sensitivity was found in type-1 diabetic patients [12].…”

Section: Discussionsupporting

confidence: 80%

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Hypoglycemia-Dependent β<sub>2</sub>-Adrenoceptor Downregulation: A Contributing Factor to Hypoglycemia Unawareness in Patients with Type-1 Diabetes?

Schwab

Menche

Schmeisl³

2004

Horm Res Paediatr

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To evaluate the influence of the incidence and unawareness of hypoglycemia on lymphocyte β₂-adrenoceptor densities, we measured β₂-adrenoceptor density using [¹²⁵I]-iodocyanopindolol and CGP 12177 before and after 1 week of treatment optimization in 33 adults with type-1 diabetes mellitus. Diabetes treatment of all patients was modified to improve their glycemic control. During this week, all patients had to complete a protocol with 7 daily glucose measurements, one of which was at night. The subjective symptoms were evaluated in case of hypoglycemia. A significant correlation between a hypoglycemia incidence below (but not above) the threshold of 2.75 mmol/l (50 mg/dl) and β₂-adrenoceptor densities on lymphocytes was found after the study week (r = –0.72, p < 0.00001). Nine patients suffering from hypoglycemia unawareness had a significantly higher incidence of hypoglycemia (p < 0.002) and lower β₂-adrenoceptor densities on lymphocytes compared to 24 patients who recognized all of their hypoglycemic episodes (p < 0.004). We conclude that downregulation of β₂-adrenoceptor densities on lymphocytes occurs as a result of recurrent hypoglycemia defined as glucose levels of <2.75 mmol/l. β₂-Adrenoceptor densities are decreased in patients with subjective hypoglycemia unawareness and might contribute to the reduced β-adrenergic sensitivity in this subgroup of patients.

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Section: Discussionsupporting

confidence: 80%

“…It is well established that acidosis and hypoglycemia are the most potent stimulators of catecholamine surges and repetitive increases in catecholamine levels lead to desensitization of sympathoadrenal signalling [25]. Lymphocytes can easily be obtained, have a long half-life and are directly exposed to plasma catecholamines.…”

Section: Discussionmentioning

confidence: 99%

Hypoglycemia-Dependent β<sub>2</sub>-Adrenoceptor Downregulation: A Contributing Factor to Hypoglycemia Unawareness in Patients with Type-1 Diabetes?

Schwab

Menche

Schmeisl³

2004

Horm Res Paediatr

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“…27,72 And finally, prolonged stimulation results in receptor downregulation, ie, a reduction in receptor number. 73 In summary, ␤-receptor signaling is a multifaceted process, and our current understanding seems still incomplete.…”

Section: Compartmentation Of ␤-Adrenergic Signalingmentioning

confidence: 99%

What Is the Role of β-Adrenergic Signaling in Heart Failure?

Lohse

Engelhardt²,

Eschenhagen³

2003

Circulation Research

708

583

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Abstract-This review addresses open questions about the role of ␤-adrenergic receptors in cardiac function and failure.Cardiomyocytes express all three ␤-adrenergic receptor subtypes-␤ 1 , ␤ 2 , and, at least in some species, ␤ 3 . The ␤ 1 subtype is the most prominent one and is mainly responsible for positive chronotropic and inotropic effects of catecholamines. The ␤ 2 subtype also increases cardiac function, but its ability to activate nonclassical signaling pathways suggests a function distinct from the ␤ 1 subtype. In heart failure, the sympathetic system is activated, cardiac ␤-receptor number and function are decreased, and downstream mechanisms are altered. However, in spite of a wealth of data, we still do not know whether and to what extent these alterations are adaptive/protective or detrimental, or both. Clinically, ␤-adrenergic antagonists represent the most important advance in heart failure therapy, but it is still debated whether they act by blocking or by resensitizing the ␤-adrenergic receptor system. Newer experimental therapeutic strategies aim at the receptor desensitization machinery and at downstream signaling steps.

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“…Regulation of GPCR transcription and post-transcriptional processes such as splicing and mRNA degradation involves complex cellular mechanisms all fine tuning the receptor resonsiveness (for review see Danner and Lohse 1999). Thus, numerous polymorphisms have been identified within the putative promoter regions, 5' and 3' untranslated (UTR) regions, and introns of GPCR genes (for review see Rana et al 2001).…”

Section: Transcriptional Levelmentioning

confidence: 99%

The structural basis of g-protein-coupled receptor function and dysfunction in human diseases

Schöneberg

Schulz²,

Gudermann

Reviews of Physiology, Biochemistry and Pharmacology

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Regulation of β-Adrenergic receptor responsiveness modulation of receptor gene expression

Cited by 10 publications

References 183 publications

Hypoglycemia-Dependent β<sub>2</sub>-Adrenoceptor Downregulation: A Contributing Factor to Hypoglycemia Unawareness in Patients with Type-1 Diabetes?

Hypoglycemia-Dependent β<sub>2</sub>-Adrenoceptor Downregulation: A Contributing Factor to Hypoglycemia Unawareness in Patients with Type-1 Diabetes?

What Is the Role of β-Adrenergic Signaling in Heart Failure?

The structural basis of g-protein-coupled receptor function and dysfunction in human diseases

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