scholarly journals Estrogenic Action on Arterial Smooth Muscle: Permissive for Maintenance of CRHR2 Expression

Endocrinology ◽  
2012 ◽  
Vol 153 (4) ◽  
pp. 1915-1924 ◽  
Author(s):  
Shan Wang ◽  
Xiaoyan Zhu ◽  
Binhai Cong ◽  
Xingji You ◽  
Yangkai Wang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Smooth Muscle Cells ◽  
Protein Kinase A ◽  
Muscle Cells ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Ovx Rats ◽  
Kinase A

Urocortin (Ucn), a member of CRH family, has been implicated to be one of the endogenous regulators in the cardiovascular system and exerts its effects locally via an autocrine/paracrine fashion. Previous studies have shown the gender difference in CRH-induced vasodilation in human skin, which is related to the concentration of estrogens during the menstrual cycle. The aim of this study was to investigate whether estrogens modulate Ucn/CRH receptor type 2 (CRHR2) expression in vascular smooth muscle, thereby leading to vasodilation. We performed sham operation or bilateral ovariectomy (OVX) on female Sprague Dawley rats. OVX rats were sc administered 17β-estradiol (E2) at a dose of 30 μg/kg·d or with placebo for 12 wk. Primary smooth muscle cells of aorta were used for the in vitro study. It was found that the Ucn-induced vasodilation and CRHR2 expression were decreased in OVX rats and restored by E2 replacement treatment for 12 wk. E2 increased the expression of CRHR2 in cultured smooth muscle cells, which was blocked by estrogen receptor-β antagonist. Ucn significantly suppressed the phenylephrine-induced phospholipase Cβ3 activation, inositol 1,4,5-trisphosphate (IP3) production, and intracellular Ca2+ elevation. Ucn stimulated the expression of active GTP-bound Gαs protein and cAMP production. The suppressive effects of Ucn on phenylephrine-induced IP3 production and intracellular Ca2+ elevation were blocked by the inhibitors of adenylate cyclase and protein kinase A. Our results demonstrate that estrogen maintains the expression of CRHR2 in aorta smooth muscle, thereby enhancing vasodilator actions of Ucn. Ucn exerts its vasorelaxant effects via Gαs-cAMP-protein kinase A signaling, leading to down-regulation of the phospholipase Cβ-IP3-Ca2+ signaling pathway.

Antimitogenic Effects of Trapidil In Coronary Artery Smooth Muscle Cells by Direct Activation of Protein Kinase A

1998 ◽  
Vol 54 (2) ◽  
pp. 241-248 ◽  
Author(s):  
Detlef Bönisch ◽  
Artur-Aron Weber ◽  
Michael Wittpoth ◽  
Michael Osinski ◽  
Karsten Schrör
Keyword(s):  
Smooth Muscle ◽  
Coronary Artery ◽  
Protein Kinase ◽  
Smooth Muscle Cells ◽  
Protein Kinase A ◽  
Muscle Cells ◽  
Direct Activation ◽  
Kinase A

Phospholipase C and adenylate cyclase signalling systems in the action of hCG on porcine myometrial smooth muscle cells

1996 ◽  
Vol 148 (1) ◽  
pp. 175-180 ◽  
Author(s):  
J Kisielewska ◽  
A P F Flint ◽  
A J Ziecik
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Smooth Muscle Cells ◽  
Protein Kinase A ◽  
Muscle Cells ◽  
Target Tissue ◽  
Myometrial Cells ◽  
Kinase C ◽  
Kinase A

Abstract Although the uterus is a target tissue for LH and its homologue hCG the second messenger system responding to LH/hCG in myometrial cells is not established. In this study we investigated the involvement of protein kinase A and protein kinase C in the action of hCG on porcine myometrial smooth muscle cells in vitro. Myometrium was obtained from ovariectomized gilts given 2·5 mg oestradiol benzoate plus 50 mg progesterone for five consecutive days. Myometrial cells were cultured for 48 h and different doses of hCG were then added. Increasing doses of hCG stimulated concentration-dependent increases in [3H]inositol phosphates (IPs) accumulation in incubations lasting 24 h. The highest dose of hCG (1000 mU/ml) increased turnover of IPs by 2·4-fold as reflected in elevations in IP1, IP2 and IP3, and similar effects were observed with noradrenaline. The time- and concentration-dependent effects of hCG on IPs accumulation occurred between 16 and 24 h of incubation. Incubation of myocytes with the lowest doses of hCG (0·1 and 1 mU/ml) caused a significant increase in cAMP accumulation but the highest doses (10–1000 mU/ml) had no effect on cAMP concentrations. This is the first demonstration that LH/hCG receptor signalling leads to increased inositol phosphate turnover in myometrial cells as well as cAMP generation and it leads to the conclusion that both protein kinase A and protein kinase C signalling mechanisms are involved in gonadotrophin action in porcine myometrial smooth muscle cells. Journal of Endocrinology (1996) 148, 175–180

scholarly journals Tonic Protein Kinase A-Dependent Effects on KV Channels in Mesenteric Smooth Muscle Cells

2011 ◽  
Vol 100 (3) ◽  
pp. 105a
Author(s):  
Jenny L. Brignell ◽  
Noel W. Davies ◽  
Carl P. Nelson ◽  
R.A.J. Challiss ◽  
Matthew P. Perry
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Smooth Muscle Cells ◽  
Protein Kinase A ◽  
Muscle Cells ◽  
Kv Channels ◽  
Kinase A

Dual inhibitory effects of dopamine on Na+ homeostasis in rat aorta smooth muscle cells

1997 ◽  
Vol 272 (2) ◽  
pp. C428-C438 ◽  
Author(s):  
M. L. Borin
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Smooth Muscle Cells ◽  
Protein Kinase A ◽  
Muscle Cells ◽  
Rat Aorta ◽  
Inhibitory Effects ◽  
Na Pump ◽  
Na Efflux ◽  
Kinase A

Dopamine is an essential catecholamine, which acts not only as a neurotransmitter in sympathetic neurons but also exhibits vasodilating and natriuretic effects in renal tubular cells, blood vessels, etc. This study describes the effect of dopamine on Na+ influx and Na+ efflux and the resulting changes in intracellular Na+ concentration ([Na+]i). [Na+]i was measured in primary cultured vascular smooth muscle cells from rat aorta with digital imaging of cells loaded with the Na+-sensitive fluorescent indicator, SBFI. Na+ influx and Na+ efflux were measured as changes in [Na+]i under the conditions of inhibition of the Na+ flux in the opposite direction. Dopamine inhibited Na+ influx in a dose-dependent manner with a maximal inhibition, approximately 45%, achieved at 10(-4) M. This effect of dopamine, as suggested by several lines of evidence, was mediated by inhibition of Na+/H+ exchange. Besides inhibition of Na+ efflux, dopamine also, with a similar potency, inhibited Na+ efflux. The latter effect was due to inhibition of the Na+ pump-mediated component of Na+ efflux, since it was not observed when Na+ pump was inhibited. Inhibition of the Na+ pump by dopamine was due to the reduction in its maximal flux and not due to the decrease in the Na+ sensitivity of the pump. Similar to dopamine, activation of protein kinase A by 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) caused inhibition of both Na+ influx and Na+ pump-mediated Na+ efflux. In contrast, activation of protein kinase C by the phorbol ester, phorbol 12,13-dibutyrate, caused activation of both Na+ influx and Na+ pump-mediated Na+ efflux. H-7, a nonspecific protein kinase inhibitor, abolished the inhibitory effects of either dopamine or 8-BrcAMP on Na+ efflux but did not affect the inhibitory effects of these compounds on Na+ influx. Dopamine either did not change [Na+]i or evoked a slight, 2-3 mM, increase in [Na+]i. Together, these results demonstrate that, in rat aortic smooth muscle cells, 1) dopamine inhibits Na+/H+ exchange-mediated Na+ influx, 2) dopamine inhibits Na+ pump-mediated Na+ efflux, 3) these effects of dopamine are mediated by an increase in cellular cAMP and, at least in the case of inhibition of the Na+ efflux, by the activation of protein kinase A, and 4) dopamine causes either small or no changes in [Na+]i, due to almost equal inhibition of Na+ influx and Na+ efflux.

scholarly journals Activation of Inward Rectifier K+ Channel 2.1 by PDGF-BB in Rat Vascular Smooth Muscle Cells through Protein Kinase A

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Chengchun Tang ◽  
Dong Wang ◽  
Erfei Luo ◽  
Gaoliang Yan ◽  
Bo Liu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Protein Kinase A ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Inward Rectifier ◽  
Kinase A ◽  
Stimulation Of

Platelet-derived growth factor-BB (PDGF-BB) can induce the proliferation, migration, and phenotypic modulation of vascular smooth muscle cells (VSMCs). We used patch clamp methods to study the effects of PDGF-BB on inward rectifier K+ channel 2.1 (Kir2.1) channels in rat thoracic aorta VSMCs (RASMCs). PDGF-BB (25 ng/mL) increased Kir2.x currents (−11.81±2.47 pA/pF, P<0.05 vs. CON, n=10). Ba2+(50 μM) decreased Kir2.x currents (−2.13±0.23 pA/pF, P<0.05 vs. CON, n=10), which were promoted by PDGF-BB (−6.98±1.03 pA/pF). PDGF-BB specifically activates Kir2.1 but not Kir2.2 and Kir2.3 channels in HEK-293 cells. The PDGF-BB-induced stimulation of Kir2.1 currents was blocked by the PDGF-BB receptor β (PDGF-BBRβ) inhibitor AG1295 and was not affected by the PDGF-BBRα inhibitor AG1296. The PDGF-BB-induced stimulation of Kir2.1 currents was blocked by the protein kinase A inhibitor Rp-8-CPT-cAMPs; however, the antagonist of protein kinase B (GSK690693) had marginal effects on current activity. The PDGF-BB-induced stimulation of Kir2.1 currents was enhanced by forskolin, an adenylyl cyclase (AC) activator, and was blocked by the AC inhibitor SQ22536. We conclude that PDGF-BB increases Kir2.1 currents via PDGF-BBRβ through activation of cAMP-PKA signaling in RASMCs.

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