scholarly journals Vascular Pharmacology of Mokuboito (Mu-Fang-Yi-Tang) and Its Constituents on the Smooth Muscle and the Endothelium in Rat Aorta

2007 ◽  
Vol 4 (3) ◽  
pp. 335-341 ◽  
Author(s):  
Seiichiro Nishida ◽  
Hiroyasu Satoh

Pharmacological actions of Mokuboito and its constituents (Sinomenium acutumand sinomenine) on rat aorta were examined. Mokuboito andS. acutumat lower concentrations (0.03–1 mg ml−1) contracted the non-loaded aorta, but at higher concentrations (1–3 mg ml−1), reversed to dilate it. The vasoconstriction was blocked by phentolamine (10 μM). Sinomenine failed to exhibit the vasoconstriction. On the other hand, Mokuboito andS. acutumdilated the NE (5 μM)-induced vasoconstriction: at 3 mg ml−1, by 98.9 ± 2.5% (n= 6,P< 0.01) and 97.0 ± 4.8% (n= 6,P< 0.01). Vasorelaxation induced by Mokuboito andS. acutumwas attenuated by indomethacin, L-NMMA and nicardipine. Propranolol decreased the vasorelaxation induced by Mokuboito, but not byS. acutum. Sinomenine also relaxed the constriction and at 100 μM, by 68.8 ± 5.1% (n= 7,P< 0.01). This vasorelaxation was attenuated by indomethacin, L-NMMA and nicardipine, and also by propranolol. Therefore, these results indicate that Mokuboito and its constituents exert both vasodilating actions mediated by endothelium-dependent mechanisms (PGI2and NO from endothelium) and by endothelium-independent mechanisms (Ca2+influx control on smooth muscle cells). Simultaneously, Mokuboito andS. acutumcause the vasoconstrictions mediated through α-adrenoceptor stimulation, but not sinomenine. Also, Mokuboito and sinomenine possess β-adrenoreceptor stimulating action, but notS. acutum.

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.


1991 ◽  
Vol 27 (9) ◽  
pp. 687-688 ◽  
Author(s):  
Ph. Andre ◽  
M. Michel ◽  
C. Schott ◽  
J. C. Stoclet

1987 ◽  
Vol 47 (2) ◽  
pp. 143-153 ◽  
Author(s):  
R. Yarom ◽  
Y. Sherman ◽  
F. Bergmann ◽  
A. Sintov ◽  
L.D. Berman

1986 ◽  
Vol 32 (2) ◽  
pp. 173-180 ◽  
Author(s):  
Maria Sjölund ◽  
Kjell Madsen ◽  
Klaus von der Mark ◽  
Johan Thyberg

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