Human airway smooth muscle expresses 7 isoforms of adenylyl cyclase: a dominant role for isoform V

Xu, Dingbang; Isaacs, Cary; Hall, Ian P.; Emala, Charles W.

doi:10.1152/ajplung.2001.281.4.l832

Cited by 22 publications

(31 citation statements)

References 37 publications

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“…At first glance, the AC isoforms expressed by hBSMC that we report appear different from those previously reported in studies of airway smooth muscle and primary cultured cells isolated from human samples (Xu et al, 2001). Xu et al (2001) detected mRNA for AC isoforms 1, 3, 4, 5, 6, 7, and 9.…”

Section: Discussioncontrasting

confidence: 99%

“…Xu et al (2001) detected mRNA for AC isoforms 1, 3, 4, 5, 6, 7, and 9. They performed immunoblot analysis on whole-cell lysates and detected expression of just AC5/6 (using the same antibody used here, which is unable to distinguish between these two isoforms).…”

Section: Discussionmentioning

confidence: 97%

“…These authors concluded that the predominant AC isoform was probably AC5, because cAMP production was inhibited by PKA activation but stimulated by treatment with phorbol ester (an activator of PKC). Given that Xu et al (2001) could not detect AC2 or AC4 by immunoblot, their conclusions were logical because AC6 activity is inhibited by PKC. However, the AC activity profile they observed could also be explained by expression of both AC2/4 with AC6, consistent with our present findings.…”

Section: Discussionmentioning

confidence: 98%

“…AC and nitric-oxide synthase activities were measured in membranes prepared from neonatal rat ventricular myocytes. Cells were rinsed twice in ice-cold phosphate- Xu et al (2001).…”

Section: Methodsmentioning

confidence: 99%

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Human Bronchial Smooth Muscle Cells Express Adenylyl Cyclase Isoforms 2, 4, and 6 in Distinct Membrane Microdomains

Bogard

Xu²,

Ostrom³

2011

J Pharmacol Exp Ther

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Adenylyl cyclases (AC) are important regulators of airway smooth muscle function, because ␤-adrenergic receptor (AR) agonists stimulate AC activity and increase airway diameter. We assessed expression of AC isoforms in human bronchial smooth muscle cells (hBSMC). Reverse transcriptase-polymerase chain reaction and immunoblot analyses detected expression of AC2, AC4, and AC6. Forskolin-stimulated AC activity in membranes from hBSMC displayed Ca 2ϩ -inhibited and G ␤␥ -stimulated AC activity, consistent with expression of AC6, AC2, and AC4. Isoproterenol-stimulated AC activity was inhibited by Ca 2ϩ but unaltered by G ␤␥ , whereas butaprost-stimulated AC activity was stimulated by G ␤␥ but unaffected by Ca 2ϩ addition. Using sucrose density centrifugation to isolate lipid raft fractions, we found that only AC6 localized in lipid raft fractions, whereas AC2 and AC4 localized in nonraft fractions. Immunoisolation of caveolae using caveolin-1 antibodies yielded Ca 2ϩ -inhibited AC activity (consistent with AC6 expression), whereas the nonprecipitated material displayed G ␤␥ -stimulated AC activity (consistent with expression of AC2 and/or AC4). Overexpression of AC6 enhanced cAMP production in response to isoproterenol and beraprost but did not increase responses to prostaglandin E 2 or butaprost. ␤ 2 AR, but not prostanoid EP 2 or EP 4 receptors, colocalized with AC5/6 in lipid raft fractions. Thus, particular G protein-coupled receptors couple to discreet AC isoforms based, in part, on their colocalization in membrane microdomains. These different cAMP signaling compartments in airway smooth muscle cells are responsive to different hormones and neurotransmitters and can be regulated by different coincident signals such as Ca 2ϩ and G ␤␥ .

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 98%

“…AC and nitric-oxide synthase activities were measured in membranes prepared from neonatal rat ventricular myocytes. Cells were rinsed twice in ice-cold phosphate- Xu et al (2001).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Human Bronchial Smooth Muscle Cells Express Adenylyl Cyclase Isoforms 2, 4, and 6 in Distinct Membrane Microdomains

Bogard

Xu²,

Ostrom³

2011

J Pharmacol Exp Ther

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“…We previously found that adenylyl cyclase V and AC6 are the major adenylyl cyclase isoforms expressed in cultured human airway smooth muscle cells (38). Thus the TNF-␣-induced sensitization of adenylyl cyclase via Raf-1-dependent pathway likely involves these adenylyl cyclase isoforms.…”

Section: Discussionmentioning

confidence: 94%

Raf-1 kinase mediates adenylyl cyclase sensitization by TNF-α in human airway smooth muscle cells

Osawa¹,

Yim²,

Xu³

et al. 2007

American Journal of Physiology-Lung Cellular and Molecular Phys

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Spatiotemporal Changes in the Gene Expression Spectrum of the β2 Adrenergic Receptor Signaling Pathway in the Lungs of Rhesus Monkeys

Zheng

Cao

et al. 2021

Lung

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Objective β2 adrenergic receptor (ADRB2) agonists mainly participate in regulation of airway function through the ADRB2-G protein-adenylyl cyclase (AC) signaling pathway; however, the key genes associated with this pathway and the spatiotemporal changes in the expression spectrum of some of their subtypes remain unclear, resulting in an insufficient theoretical basis for formulating the dose and method of drug administration for neonates. Methods We performed sampling at different developmental time points in rhesus monkeys, including the embryo stage, neonatal stage, and adolescence. The MiSeq platform was used for sequencing of key genes and some of their subtypes in the ADRB2 signaling pathway in lung tissues, and target gene expression was normalized and calculated according to reads per kilobase million. Results At different lung-developmental stages, we observed expression of phenylethanolamine N-methyltransferase (PNMT), ADRB2, AC, AKAP and EPAC subtypes (except AC8, AKAP4/5), and various phosphodiesterase (PDE) subtypes (PDE3, PDE4, PDE7, and PDE8), with persistently high expression of AC6, PDE4B, and AKAP(1/2/8/9/12/13, and EZR) maintained throughout the lung-developmental process, PNMT, ADRB2, AC(4/6), PDE4B, and AKAP(1/2/8/9/12/13, EZR, and MAP2)were highly expressed at the neonatal stage. Conclusion During normal lung development in rhesus monkeys, key genes associated with ADRB2–G protein–AC signaling and some of their subtypes are almost all expressed at the neonatal stage, suggesting that this signaling pathway plays a role in this developmental stage. Additionally, AC6, PDE4B, and AKAP(1/2/8/9/12/13, and EZR) showed persistently high expression during the entire lung-developmental process, which provides a reference for the development and utilization of key gene subtypes in this pathway.

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Human airway smooth muscle expresses 7 isoforms of adenylyl cyclase: a dominant role for isoform V

Cited by 22 publications

References 37 publications

Human Bronchial Smooth Muscle Cells Express Adenylyl Cyclase Isoforms 2, 4, and 6 in Distinct Membrane Microdomains

Human Bronchial Smooth Muscle Cells Express Adenylyl Cyclase Isoforms 2, 4, and 6 in Distinct Membrane Microdomains

Raf-1 kinase mediates adenylyl cyclase sensitization by TNF-α in human airway smooth muscle cells

Spatiotemporal Changes in the Gene Expression Spectrum of the β2 Adrenergic Receptor Signaling Pathway in the Lungs of Rhesus Monkeys

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