Involvement of cyclic nucleotides in renal artery smooth muscle relaxation

Karsten, A J; Derouet, H.; Eckert, Roger

doi:10.1007/s00240-002-0281-2

Cited by 14 publications

(9 citation statements)

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“…31 Similarly, activation of A1 receptors by adenosine constricts the renal afferent arteriole by a G i -mediated cascade involving activation of phospholipase C. 32 Reciprocally, agents that increase cAMP promote arterial vasorelaxation. 33,34 However, our data do not support a direct vasomotor effect of GPR81 activation and instead indicate dependency on ET-1 release and subsequent endothelin-A receptor activation. Notably, ET-1 is synthesized by arterial myocytes, 35 a cell that expresses GPR81.…”

Section: Discussioncontrasting

confidence: 84%

Endothelin-1 Mediates the Systemic and Renal Hemodynamic Effects of GPR81 Activation

et al. 2020

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Endothelin-1 mediates the systemic and renal hemodynamic effects of GPR81 activation', Hypertension. G PR81 (G-protein-coupled receptor 81), GPR109a, and GPR109b form the hydroxycarboxylic acid receptor subfamily. 1 Encoded by the HCAR1 gene, GPR81 is predominantly expressed in brown and white adipose tissue. 2 L-lactate is the endogenous ligand with an EC 50 of ≈5 mmol/L. 3 Lactate, formed from pyruvate during anaerobic glycolysis, has a physiological plasma concentration of 0.5 to 2 mmol/L, rising from 10 to 30 mmol/L during intense exercise or prolonged hypoxia. 4,5 This suggests that GPR81 is either physiologically quiescent basally or that it is primarily responsive to the local, rather than circulating, concentration of lactate. In adipocytes, activation of GPR81 by L-lactate prevents lipid breakdown and promotes storage of energy-rich metabolites in adipocytes. 2,6 Synthetic GPR81 agonists 7-9 are potential therapies for dyslipidemia and inhibit lipolysis in cultured adipocytes and in vivo.

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Section: Discussioncontrasting

confidence: 84%

Endothelin-1 Mediates the Systemic and Renal Hemodynamic Effects of GPR81 Activation

et al. 2020

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“…The Rho kinase pathway is therefore a possible target in this pathway; however, the specificity for α1AR would need elucidation. Furthermore, phenylephrine-mediated constriction has also been linked to activation of a G i –cAMP (adenosine 3′,5′-monophosphate)–dependent signaling pathway in rat mesenteric arteries (50, 51) and swine renal arteries (52), and pharmacological evidence has demonstrated a possible interaction between α1AR and the G i pathway in promoting cardiomyocyte contraction (53). Although our work shows that purinergic signaling is a key component to the α1AR vasoconstriction pathway, the mechanism linking α1AR stimulation and Panx1 channel opening requires more detailed analysis of the signaling pathways downstream of α1AR, 5-HT 2A , 5-HT 1B/1D , and ET A .…”

Section: Discussionmentioning

confidence: 99%

A molecular signature in the pannexin1 intracellular loop confers channel activation by the α1 adrenoreceptor in smooth muscle cells

et al. 2015

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Both purinergic signaling through nucleotides such as ATP (adenosine 5′-triphosphate) and noradrenergic signaling through molecules such as norepinephrine regulate vascular tone and blood pressure. Pannexin1 (Panx1), which forms large-pore, ATP-releasing channels, is present in vascular smooth muscle cells in peripheral blood vessels and participates in noradrenergic responses. Using pharmacological approaches and mice conditionally lacking Panx1 in smooth muscle cells, we found that Panx1 contributed to vaso-constriction mediated by the α1 adrenoreceptor (α1AR), whereas vasoconstriction in response to serotonin or endothelin-1 was independent of Panx1. Analysis of the Panx1-deficient mice showed that Panx1 contributed to blood pressure regulation especially during the night cycle when sympathetic nervous activity is highest. Using mimetic peptides and site-directed mutagenesis, we identified a specific amino acid sequence in the Panx1 intracellular loop that is essential for activation by α1AR signaling. Collectively, these data describe a specific link between noradrenergic and purinergic signaling in blood pressure homeostasis.

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“…As db-cCMP is a prodrug of cCMP, the effective EC 50 concentration of cCMP inside smooth muscle cells is lower. All further aorta experiments were performed with 300 lM db-cCMP which is in the range of concentration previously used for physiological analysis of smooth muscle with db-cAMP or db-cGMP [10,11] 27 ± 9 lM. To exclude effects of the short chain fatty acid butyrate on second messenger signalling or vasodilatation [12] we applied butyrate or tributyrin on preconstricted aortic smooth muscle tissue.…”

Section: Db-ccmp Induces Smooth Muscle Relaxationmentioning

confidence: 99%

Cyclic cytidine 3′,5′‐monophosphate (cCMP) signals via cGMP kinase I

et al. 2010

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a b s t r a c tWe analysed the function and intracellular signalling of the cyclic pyrimidinic nucleotide cCMP. The membrane-permeable cCMP analogue dibutyryl-cCMP mediated mouse aorta relaxation. cCMP activated purified cGMP-dependent protein kinase (cGK) Ia and Ib and stimulated cGK in aorta lysates. cCMP-induced relaxation was abolished in cGKI-knockout tissue. Additionally, deletion of inositoltrisphosphate receptor associated cGKI substrate (IRAG) suppressed cCMP-mediated relaxation. Signalling of cCMP via cGKI/IRAG appears to be of broader physiological importance because cCMP-mediated inhibition of platelet aggregation was absent in cGKI-and IRAG-deficient platelets. These results demonstrate that cCMP acts as intracellular messenger molecule, most unexpectedly utilizing the cGMP signal transduction pathway.

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Involvement of cyclic nucleotides in renal artery smooth muscle relaxation

Cited by 14 publications

References 0 publications

Endothelin-1 Mediates the Systemic and Renal Hemodynamic Effects of GPR81 Activation

Endothelin-1 Mediates the Systemic and Renal Hemodynamic Effects of GPR81 Activation

A molecular signature in the pannexin1 intracellular loop confers channel activation by the α1 adrenoreceptor in smooth muscle cells

Cyclic cytidine 3′,5′‐monophosphate (cCMP) signals via cGMP kinase I

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