Role of mitogen-activated protein kinase pathway in acetylcholine-mediated in vitro relaxation of rat pulmonary artery

Choy, Wing‐Yiu; Wong, Y. F.; Kwan, Yiu Wa; Au, Alice Lai Shan; Lau, Wing Hung; Raymond, Kenneth; Zuo, Zhong

doi:10.1016/s0014-2999(01)01533-3

Cited by 17 publications

(8 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This observation is consistent with other similar studies where the same (Jovanovic et al. , 1994a) or different cholinesterases inhibitor (Choy et al. , 2002) was used.…”

Section: Resultssupporting

confidence: 93%

Functional characterization of the muscarinic receptors involved in endothelium‐dependent relaxation in isolated canine uterine artery

Pesic

Grbović

Stoiljković

et al. 2009

Vet Pharm & Therapeutics

View full text Add to dashboard Cite

Acetylcholine interacts with endothelial muscarinic receptors releasing nitric oxide and causing vasodilatation. To identify the receptor subtype responsible for acetylcholine-induced relaxation in canine uterine artery, the usual organ bath method for in vitro investigation on isolated blood vessels was applied. Using a range of muscarinic receptor antagonists such as atropine (nonselective), pirenzepine (M(1)-selective), methoctramine (M(2)-selective) and p-fluoro-hexahydro-sila-difenidol (p-FHHSiD) (M(1)/M(3)) and determining pA2 value of those antagonists through Shild analysis, we aimed at establishing a precise receptor mechanism underlying acetylcholine-induced relaxation in isolated canine uterine artery. The relaxation of uterine arterial rings in response to acetylcholine in the presence or absence of selective muscarinic receptors antagonists was calculated using concentration response curves. Acetylcholine induced concentration-dependent and endothelium-dependent relaxation of arterial rings precontracted with phenylephrine (pEC(50) = 6.90 +/- 0.02). Muscarinic receptors antagonists atropine, pirenzepine, methoctramine and p-FHHSiD competitively antagonized the response to acetylcholine and obtained pA(2) values were 9.91 +/- 0.06, 6.60 +/- 0.04, 6.21 +/- 0.08 and 8.05 +/- 0.1, respectively. This study showed that acetylcholine induced endothelium-dependent relaxation of canine uterine artery by stimulation of muscarinic receptors localized on the endothelial cells. On the basis of differential antagonist affinity, we suggest that the muscarinic receptors involved in the acetylcholine-induced relaxation of canine uterine artery are predominantly of M(3) subtype.

show abstract

“…This observation is consistent with other similar studies where the same (Jovanovic et al. , 1994a) or different cholinesterases inhibitor (Choy et al. , 2002) was used.…”

Section: Resultssupporting

confidence: 93%

Functional characterization of the muscarinic receptors involved in endothelium‐dependent relaxation in isolated canine uterine artery

Pesic

Grbović

Stoiljković

et al. 2009

Vet Pharm & Therapeutics

View full text Add to dashboard Cite

show abstract

“…AChE is a mediator of cholinergic signaling that has also been associated with RAS signal transduction. It may be a downstream target of RAS signaling in PC12 cells [40,41]; on the other hand AChE may induce RAS activity in smooth muscle cells [42]. It is currently not known whether similar connections exist in colon epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Acetylcholinesterase supports anchorage independence in colon cancer

Syed

Fenoglio‐Preiser

Skau

et al. 2008

Clin Exp Metastasis

View full text Add to dashboard Cite

Various roles have been attributed to Acetylcholinesterase (AChE) in cancer. Evidence exists for a pro-apoptotic function, consistent with a protective role of AChE. Because other reports suggested that upregulated AChE in some tumors may control cell adhesion, we tested the effects of AChE on anchorage independence (an essential component of metastasis) of colon tumor cells. Several AChE inhibitors dose-dependently suppressed colony formation of HTB-38 cells in soft agar. This effect of AChE was confirmed with HTB-38 cells stably overexpressing AChE. In contrast, cell proliferation was not altered by the effective doses of these chemical inhibitors or by transfected AChE. Protection from cell cycle arrest consecutive to cancer cell detachment may be conveyed by changes in cell-matrix interactions. Reflective of such changes, the AChE overexpressing cells adhered more strongly to Fibronectin than did the vector controls. The AChE-dependent adhesion was RGD-dependent and accompanied by increased c-Myb DNA-binding, suggesting that AChE upregulates an Integrin receptor via c-Myb. In support of these observations, we find AChE message and protein to be expressed in a large fraction of colon cancers and in all colon tumor cell lines analyzed, but only rarely in normal colon specimens. Our results imply a dual role for AChE in colon cancer. While the anti-apoptotic effects of AChE may be protective against early stages of tumorigenesis, this gene product may support the later stages of transformation by enhancing anchorage independent growth. The induction of Integrins could render the cells independent of microenvironmental cues and override cell cycle arrest after deadhesion.

show abstract

“…Resting tension was readjusted, if necessary, before commencing the experiments. Relaxation in response to relaxant was expressed as % of phenylephrine (1 AM)-induced tone (0.32 T 0.05 g) (a sustained arterial contraction which is 90% of maximum contraction produced by 3 AM phenylephrine) (Choy et al, 2002), and 100% relaxation was considered when active tone returned to baseline level. Manoeuvres such as administration of N G -nitro-l-arginine methyl-ester (l-NAME), iberiotoxin, 4-aminopyridine and endothelium denudation resulted in an enhanced phenylephrine (1 AM)-induced tone (33.6 T 4.9% increase), concentration of phenylephrine used was therefore adjusted accordingly (0.4 -0.7 AM) in order to have a similar magnitude of active tone developed.…”

Section: Tissue Preparation and Isometric Tension Measurementsmentioning

confidence: 99%

“…Only one concentration of individual drug was tested in each cell. Where stated, concentration of inhibitors employed in this study was the reported effective concentration of individual agent, based on our previous studies (Kwan et al, 1999;Choy et al, 2002;Au et al, 2003) and other group (Zhao et al, 2001), tested on pulmonary and other vascular smooth muscle preparations.…”

Section: Enzymatic Dissociation Of Pulmonary Artery Smooth Muscle Celmentioning

confidence: 99%

Contribution of glibenclamide-sensitive, ATP-dependent K+ channel activation to acetophenone analogues-mediated in vitro pulmonary artery relaxation of rat

Seto

Hui

et al. 2006

Life Sciences

Self Cite

View full text Add to dashboard Cite

Role of mitogen-activated protein kinase pathway in acetylcholine-mediated in vitro relaxation of rat pulmonary artery

Cited by 17 publications

References 34 publications

Functional characterization of the muscarinic receptors involved in endothelium‐dependent relaxation in isolated canine uterine artery

Functional characterization of the muscarinic receptors involved in endothelium‐dependent relaxation in isolated canine uterine artery

Acetylcholinesterase supports anchorage independence in colon cancer

Contribution of glibenclamide-sensitive, ATP-dependent K+ channel activation to acetophenone analogues-mediated in vitro pulmonary artery relaxation of rat

Contact Info

Product

Resources

About