Role of Phosphatidylinositol Turnover in the Contraction of the Rat Aorta

Author(s):  
Evangeline D. Motley ◽  
Robert R. Ruffolo ◽  
Douglas W. P. Hay ◽  
Andrew J. Nichols
Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1144 ◽  
Author(s):  
Sergei K. Trufanov ◽  
Elena Yu. Rybakova ◽  
Piotr P. Avdonin ◽  
Alexandra A. Tsitrina ◽  
Irina L. Zharkikh ◽  
...  

Second messenger nicotinic acid adenine dinucleotide phosphate (NAADP) triggers Ca2+ release via two-pore channels (TPCs) localized in endolysosomal vesicles. The aim of the present work is to evaluate the role of TPCs in the action of norepinephrine (NE), angiotensin II (AngII), vasopressin (AVP), and 5-hydroxytriptamine (5-HT) on free cytoplasmic calcium concentration ([Ca2+]i) in smooth muscle cells (SMCs) isolated from rat aorta and on aorta contraction. To address this issue, the NAADP structural analogue and inhibitor of TPCs, NED 19, was applied. We have demonstrated a high degree of colocalization of the fluorescent signals of cis-NED 19 and endolysosmal probe LysoTracker in SMCs. Both cis- or trans-NED 19 inhibited the rise of [Ca2+]i in SMCs induced by 100 μM NE by 50–60%. IC50 for cis- and trans-NED 19 were 2.7 and 8.9 μM, respectively. The inhibition by NED 19 stereoisomers of the effects of AngII, AVP, and 5-HT was much weaker. Both forms of NED 19 caused relaxation of aortic rings preconstricted by NE, with relative potency of cis-NED 19 several times higher than that of trans-NED 19. Inhibition by cis-NED 19 of NE-induced contraction was maintained after intensive washing and slowly reversed within an hour of incubation. Cis- and trans-NED 19 did not cause decrease in the force of aorta contraction in response to Ang II and AVP, and only slightly relaxed aorta preconstricted by 5-HT and by KCl. Suppression of TPC1 in SMCs with siRNA caused a 40% decrease in [Ca2+]i in response to NE, whereas siRNA against TPC2 did not change NE calcium signaling. These data suggest that TPC1 is involved in the NE-stimulated [Ca2+]i rise in SMCs. Inhibition of TPC1 activity by NED 19 could be the reason for partial inhibition of aortic rings contraction in response to NE.


1999 ◽  
Vol 81 (4) ◽  
pp. 362-366 ◽  
Author(s):  
Hiroyuki Kinoshita ◽  
Shizue Iwahashi ◽  
Tetsuya Kakutani ◽  
Kazuhiro Mizumoto ◽  
Hiroshi Iranami ◽  
...  
Keyword(s):  

2003 ◽  
Vol 458 (1-2) ◽  
pp. 145-154 ◽  
Author(s):  
Ayotunde S.O Adeagbo ◽  
Darshana Patel ◽  
Abdallah Iddrissu ◽  
John Walker ◽  
Sridhar Thirumalai ◽  
...  
Keyword(s):  

1992 ◽  
Vol 58 ◽  
pp. 194
Author(s):  
Toshio Nakaki ◽  
Yukari Otsuka ◽  
Misa Nakayama ◽  
Ryuichi Kato
Keyword(s):  

2011 ◽  
Vol 64 (3) ◽  
pp. 274-282 ◽  
Author(s):  
Vivek Khanna ◽  
Manish Jain ◽  
Manoj Kumar Barthwal ◽  
Diganta Kalita ◽  
Jeena Jyoti Boruah ◽  
...  

Science ◽  
1986 ◽  
Vol 232 (4746) ◽  
pp. 87-90 ◽  
Author(s):  
BC Berk ◽  
RW Alexander ◽  
TA Brock ◽  
MA Gimbrone ◽  
RC Webb

Platelet-derived growth factor (PDGF) is a potent mitogen for vascular smooth muscle cells that has been implicated in the pathogenesis of atherosclerosis. The potential role of PDGF in the altered vasoreactivity of atherosclerotic vessels has been studied through an examination of its effects on contractility in the rat aorta. PDGF caused a concentration-dependent contraction of aortic strips and was significantly more potent on a molar basis than the classic vasoconstrictor peptide angiotensin II. Furthermore, PDGF increased the cytosolic free calcium concentration in cultured rat aortic smooth muscle cells. These observations suggest a new biological activity for PDGF that may contribute to the enhanced vasoreactivity of certain atherosclerotic vessels.


1979 ◽  
Vol 178 (3) ◽  
pp. 681-687 ◽  
Author(s):  
Shamshad Cockcroft ◽  
Bastien D. Gomperts

Histamine secretion and phosphatidylinositol turnover were compared in antigen-sensitized rat peritoneal mast cells stimulated with a number of different ligands. A small and variable increase in the incorporation of [32P]Pi and of [3H]inositol into phosphatidylinositol was observed when the cells were treated with immunoglobulin E-directed ligands (antigens and concanavalin A), and this was accompanied by a low amount of secretion (<10% of total cell histamine). In the presence of added phosphatidylserine, the addition of immunoglobulin E-directed ligands invariably led to an enhanced rate (approx. 4-fold) of labelling of phosphatidylinositol and, in the presence of Ca2+, this was accompanied by the secretion of histamine. The labelling of phosphatidylinositol and histamine secretion were also stimulated by chymotrypsin and compound 48/80. Whereas the phosphatidylinositol response did not require the presence of extracellular Ca2+, the secretion of histamine was either enhanced or dependent on extracellular Ca2+ (depending on the ligand used). The dependence on ligand concentration for the phosphatidylinositol response and histamine secretion were similar. The increased isotopic incorporation into phosphatidylinositol continued for about 1h although histamine secretion (elicited with concanavalin A) stopped within 2min. These results support the proposition that metabolic events involving phosphatidylinositol play a necessary intermediate role in the regulation of Ca2+ channels by ligand-activated receptors.


2000 ◽  
Vol 82 ◽  
pp. 184
Author(s):  
Akira Ishihata ◽  
Katsunari Tasaki ◽  
Yoshiko Inuzuka ◽  
Yumi Katano

1999 ◽  
Vol 79 ◽  
pp. 193
Author(s):  
Michiko Iwasaki ◽  
Shunichi Shimizu ◽  
Masakazu Ishii ◽  
Yutaka Kawakami ◽  
Kazutaka Momose ◽  
...  
Keyword(s):  

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