Mechanisms regulating cAMP-mediated growth of bovine neonatal pulmonary artery smooth muscle cells

Guldemeester, Alexandra; Stenmark, Kurt R.; Brough, George H.; Stevens, Troy

doi:10.1152/ajplung.1999.276.6.l1010

Cited by 6 publications

(4 citation statements)

References 35 publications

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“…17 Conversely, we demonstrated consistent inhibition of DNA synthesis and proliferation after direct and indirect stimulation of intracellular cAMP production in human PASMCs. Bovine vascular SMCs are also reported to develop tolerance to the antimitogenic actions of iloprost over 24 hours.…”

Section: Discussionmentioning

confidence: 58%

“…15 In contrast, the effects of PGI 2 and its analogues on pulmonary artery SMC (PASMC) growth are less certain, with vasodilatory prostaglandins having been found to stimulate rather than inhibit the proliferation of bovine PASMCs. 16,17 Therefore, we sought to establish whether the stable PGI 2 analogues iloprost and cicaprost could influence the growth of human PASMCs derived from distal and proximal regions of the pulmonary artery tree.…”

mentioning

confidence: 99%

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Prostacyclin Analogues Differentially Inhibit Growth of Distal and Proximal Human Pulmonary Artery Smooth Muscle Cells

et al. 2000

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Section: Discussionmentioning

confidence: 58%

mentioning

confidence: 99%

Prostacyclin Analogues Differentially Inhibit Growth of Distal and Proximal Human Pulmonary Artery Smooth Muscle Cells

et al. 2000

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“…AC2 (10,33), AC3 (46,48), AC4 (11), AC5 (33), AC6 (33), and AC7 (43) have been detected in whole lung RNA preparations by either Northern blot or RT-PCR in various animals; however, few previous studies have addressed the localization of AC isoforms within the lung. Guldemeester et al (13) previously showed medial staining of AC2 in small and large neonatal and adult bovine pulmonary arteries. AC2, AC4, AC6, and AC7 mRNAs were detected in bovine pulmonary artery endothelial cells (39).…”

Section: Discussionmentioning

confidence: 90%

Characterization of adenylyl cyclase isoforms in rat peripheral pulmonary arteries

Jourdan

Mason

Lü

et al. 2001

American Journal of Physiology-Lung Cellular and Molecular Phys

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Activation of adenylyl cyclase (AC), of which there are 10 diversely regulated isoforms, is important in regulating pulmonary vascular tone and remodeling. Immunohistochemistry in rat lungs demonstrated that AC2, AC3, and AC5/6 predominated in vascular and bronchial smooth muscle. Isoforms 1, 4, 7, and 8 localized to the bronchial epithelium. Exposure of animals to hypoxia did not change the pattern of isoform expression. RT-PCR confirmed mRNA expression of AC2, AC3, AC5, and AC6 and demonstrated AC7 and AC8 transcripts in smooth muscle. Western blotting confirmed the presence of AC2, AC3, and AC5/6 proteins. Functional studies provided evidence of cAMP regulation by Ca(2+) and protein kinase C-activated but not G(i)-inhibited pathways, supporting a role for AC2 and a Ca(2+)-stimulated isoform, AC8. However, NKH-477, an AC5-selective activator, was more potent than forskolin in elevating cAMP and inhibiting serum-stimulated [(3)H]thymidine incorporation, supporting the presence of AC5. These studies demonstrate differential expression of AC isoforms in rat lungs and provide evidence that AC2, AC5, and AC8 are functionally important in cAMP regulation and growth pathways in pulmonary artery myocytes.

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“…Previous studies on arterial smooth muscle from different species have demonstrated expression of multiple AC isoforms. AC2, AC4, AC5/6, and AC7, but not AC3, have been found in bovine pulmonary artery SMCs (30,31). Rat aortic SMCs have been shown to express AC3 and possibly AC8 but not the neuronal AC1 (32).…”

Section: Ac3 Mediates the Growth-inhibitory Effects Of Pge 2 Inmentioning

confidence: 96%

Adenylyl Cyclase 3 Mediates Prostaglandin E2-induced Growth Inhibition in Arterial Smooth Muscle Cells

Wong¹,

Baker²,

Trinh³

et al. 2001

Journal of Biological Chemistry

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Arterial smooth muscle cell (SMC) proliferation contributes to a number of vascular pathologies. Prostaglandin E 2 (PGE 2 ), produced by the endothelium and by SMCs themselves, acts as a potent SMC growth inhibitor. The growth-inhibitory effects of PGE 2 are mediated through activation of G-protein-coupled membrane receptors, activation of adenylyl cyclases (ACs), formation of cAMP, and subsequent inhibition of mitogenic signal transduction pathways in SMCs. Of the 10 different mammalian AC isoforms known today, seven isoforms (AC2-7 and AC9) are expressed in SMCs from various species. We show that, despite the presence of several different AC isoforms, the principal AC isoform activated by PGE 2 in human arterial SMCs is a calmodulin kinase II-inhibited AC with characteristics similar to those of AC3. AC3 is expressed in isolated human arterial SMCs and in intact aorta. We further show that arterial SMCs isolated from AC3-deficient mice are resistant to PGE 2 -induced growth inhibition. In summary, AC3 is the principal AC isoform activated by PGE 2 in arterial SMCs, and AC3 mediates the growth-inhibitory effects of PGE 2 . Because AC3 activity is inhibited by intracellular calcium through calmodulin kinase II, AC3 may serve as an important integrator of growth-inhibitory signals that stimulate cAMP formation and growth factors that increase intracellular calcium.

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Mechanisms regulating cAMP-mediated growth of bovine neonatal pulmonary artery smooth muscle cells

Cited by 6 publications

References 35 publications

Prostacyclin Analogues Differentially Inhibit Growth of Distal and Proximal Human Pulmonary Artery Smooth Muscle Cells

Prostacyclin Analogues Differentially Inhibit Growth of Distal and Proximal Human Pulmonary Artery Smooth Muscle Cells

Characterization of adenylyl cyclase isoforms in rat peripheral pulmonary arteries

Adenylyl Cyclase 3 Mediates Prostaglandin E2-induced Growth Inhibition in Arterial Smooth Muscle Cells

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