• 沒有找到結果。

台灣款冬 (Petasites formosanus Kitamura) 成分 Petasins 在離體 天竺鼠氣管的鬆弛作用

N/A
N/A
Info
下載
Protected

Academic year: 2021

Share "台灣款冬 (Petasites formosanus Kitamura) 成分 Petasins 在離體 天竺鼠氣管的鬆弛作用"

Copied!
2
0
0

加載中.... (立即查看全文)

立即下載 ( 2 頁 )

全文

(1)

台灣款冬 (Petasites formosanus Kitamura) 成分 Petasins 在離體 天竺鼠氣管的鬆弛作用

我們分析台灣款冬 (Petasites formosanus Kitamura) 所抽提的 petasins 類化合物，

包括 petasi 、 iso-petasin 、 S-petasin 與 iso-S-petasin 對氣管的鬆弛活性，上述 pet

asins 類化合物對 histamine (10 mM) 、 carbachol (0.2 mM) 、 KCl (30 mM) 及 leukotr

iene D4 (10 nM) 預縮的離體天竺鼠氣管，產生濃度依存性的鬆弛作用， S-petasin 雖對

四種收縮劑無特殊的選擇性，但 iso-S-petasin 對 carbachol 和 KCl 預縮的鬆弛作用

較具有選擇性，它們的 IC50 都在 10 mM 左右，就構造 - 活性之關係而言，含有硫原子的

petasins 對氣管的鬆弛活性強度 (potency) 比沒有硫原子的 petasins 要強。上述 pe

tasins 類化合物中，除了 iso-S-petasin (50?200 mM) 使 carbachol 之對數濃度─反

應曲線平行向右移動，且不改變其最大收縮，顯示具抗毒蕈素 (antimuscarinic effect)

之競爭作用外， S-petasin (10?200 mM) 或 iso-S-petasin (10?200 mM) ，均非競爭

性地抑制 histamine 、 carbachol 或 KCl 累加引起之收縮，在無鈣環境中， S-petasin 或

iso-S-petasin 預處理對 histamine (100 mM) 、 carbachol (10 mM) 或 KCl (60 mM)

去極化因累加外鈣引起的收縮能非競爭性地抑制﹔在完全無鈣 ( 含 0.02 mM EGTA) 環境中

，兩者預處理對 histamine 或 carbachol 累加引起之收縮亦能非競爭性地抑制，顯示兩

者對細胞外鈣離子流入或者細胞內鈣離子釋放都有抑制作用。對 carbachol (0.2 mM) 預

縮而 nifedipine (10 mM) 引起的最大鬆弛情況下， S-petasin 或 iso-S-petasin 也會

產生更進一步的鬆弛，表示不管有無抑制 voltage 及 / 或 receptor operated calcium c

hannels ，一定尚有其他的鬆弛機轉。然而其鬆弛反應不受 Nw-nitro-L-arginine (20 mM

) 、 a-chymotrypsin (1 U/ml) 、 propranolol (1 mM) 、 glibenclamide (10 mM) 、 methyle

ne blue (25 mM) 及 2',5'-dideoxyadenosine (10 mM) 存在的影響，表示其鬆弛作用與

nitric oxide 、 vasoactive intestinal polypeptide 、 b-adrenoceptor 受體活化、 ATP-

敏感的鉀通道開啟、 adenylate cyclase 或 guanylate cyclase 活化無關。 S-petasin (

10?20 mM) 或 iso-S-petasin (10?20 mM) 不能使 forskolin 及 sodium nitroprussi

de 的對數濃度─反應曲線濃度依存性地向左移動，亦不能增加 forskolin 及 sodium ni

troprusside 的 pD2 值，由 phosphodiesterase (PDE) 活性的直接測定，得知 S-petas

in (100?300 mM) 能有意義地抑制 cAMP-dependent PDE 的活性，但最高只能抑制 33.94

±6.06 % (n=5) ，顯示 S-petasin 只有輕微的抑制作用，而 iso-S-petasin (30?300 m

M) 不能有意義地抑制此酵素， S-petasin 及 iso-S-petasin (3?300 mM) 亦不能有意義

地抑制 cGMP-dependent PDE 的活性。綜合以上結果，兩者對細胞外鈣離子流入或者細胞

內鈣離子釋放都有抑制作用， iso-S-petasin 具有較強的抗毒蕈素作用，而 S-petasin 對

cAMP-dependent PDE 只有輕微的抑制作用。

(2)

Relaxant effects of petasins, ingredients of Petasites formosanus Kitamura in isolated guinea-pig trachea

Four petasins, including petasin, iso-petasin, S-petasin and iso-S-petasin, we re isolated from Petasites formosanus Kitamura. They concentration-dependently relaxed histamine (10 *M)-, carbachol (0.2 *M)-, KCl (30 mM)- or leukotriene D4 (10 nM)-induced precontractions of isolated guinea-pig trachealis. Iso-S-pe tasin selectively relaxed carbachol- and KCl-induced precontractions, although S-petasin non-selectively relaxed the precontractions induced by these contra ctile agents. Their IC50s were approximately about 10 mM. It seems that the re laxant effects of sulfur containing petasins, S-petasin and iso-S-petasin, wer e more potent than those of non-sulfur containg petasins, petasin and iso-peta sin.The preincubation of S-petasin or iso-S-petasin non-competitively inhibite d contractions induced by cumulatively adding histamine, carbachol and KCl in isolated guinea-pig trachealis, with an exception that the preincubation of is o-S-petasin (50~200 *M) competitively inhibited cumulative carbachol-induced c ontractions, suggesting that iso-S-petasin had an antimuscarinic effect. Both S-petasin and iso-S-petasin had a selectively inhibitory effect on cumulative KCl-induced contractions. In Ca2+-free medium, preincubation of S-petasin or i so-S-petasin non-competitively inhibited cumulative Ca2+-induced contractions in histamine (100 mM)-, carbachol (10 mM)- or KCl (60 mM)-depolarized tracheal is. In Ca2+-free medium containing 0.02 mM EGTA, the incubations of S-petasin and iso-S-petasin also non-competitively inhibited cumulative histamine- or ca rbachol-induced contractions. The above results suggest that S-petasin and iso -S-petasin may inhibit Ca2+-influx from extracellular space and Ca2+-release f rom intracellular Ca2+ stores. In normal Ca2+-medium, S-petasin was significan tly more potent than iso-S-petasin on the inhibition of Ca2+-influx from extra cellular space and Ca2+-release from intracellular Ca2+ stores induced by hist amine. However, iso-S-petasin was significantly more potent than S-petasin on the inhibition of Ca2+-influx from extracellular space via receptor (ROC) and/

or voltage operated calcium channels (VOC), which were opened by carbachol-dep olarization in Ca2+-free medium. After a maximal inhibition on carbachol (0.2

*M)-induced precontraction by nifedipine (10 *M), S-petasin or iso-S-petasin c

aused a further relaxation of the trachealis. The result suggests S-petasin an

d iso-S-petasin may have other relaxant mechanisms regardless of whether inhib

iting VOC in the trachealis. However, their relaxant effects were not affected

by the presence of propranolol (1 *M), 2*,5*-dideoxyadenosine (10 *M), methyl

ene blue (25 *M), glibenclamide (10 *M), Nw-nitro-L-arginine (20 *M) or *-chym

otrypsin (1 U/ml). It suggests their relaxing effect may be unrelated to activ

ation of *-adrenoceptor, adenylate cyclase or guanylate cyclase, the opening o

f ATP-sensitive potassium channels and the liberation of nitric oxide (NO) or

vasoactive intestinal polypeptide (VIP).S-petasin and iso-S-petasin (10~20 *M)

did not produce a parallel leftward shift of the log concentration-response c

urves of forskolin and sodium nitroprusside. They did not affect pD2 values of

forskolin and sodium nitroprusside. Neither cAMP- nor cGMP-dependent phosphod

iesaterase (PDE) activity was inhibited by S-petasin and iso-S-petasin, except

that S-petasin (100~300 *M) had a slightly inhibitory effect on cAMP-dependen

t PDE activity. The maximal inhibition on the enzyme was only 33.94 * 6.06 % (

n=5). In conclusion, S-petasin and iso-S-petasin inhibited both Ca2+-influx fr

om extracellular space and Ca2+-release from intracellular stores. In addition

, iso-S-petasin had an antimuscarinic effect and S-petasin slightly inhibited

cAMP-dependent PDE.

參考文獻

立即下載 ( PPT - 2 頁 - 142.00 KB )

相關文件

s[In The Concept of Nirvāna in Mādhyamika

6 《中論·觀因緣品》，《佛藏要籍選刊》第 9 冊，上海古籍出版社 1994 年版，第 1

On Algebraic Independence of Special Zeta Values in Characteristic p

To proceed, we construct a t-motive M S for this purpose, so that it has the GP property and its “periods”Ψ S (θ) from rigid analytic trivialization generate also the field K S ,

Economics Curriculum and Assessment Guide (Secondary 4-6)

 Students are expected to explain the effects of change in demand and/or change in supply on equilibrium price and quantity, with the aid of diagram(s). Consumer and producer

Areas to be covered in the talk

Now, nearly all of the current flows through wire S since it has a much lower resistance than the light bulb. The light bulb does not glow because the current flowing through it

Evaluation of the Enhanced Native-speaking English Teacher Scheme in Hong Kong Secondary Schools 2009 Submitted to Education Bureau Hong Kong

More than 90% of the leaders reported that the Panel Chair was also expected to ensure that all teachers followed curriculum guidelines, and to review evidence of teaching

2 Overview and Contributions of the Paper

Wang, Solving pseudomonotone variational inequalities and pseudocon- vex optimization problems using the projection neural network, IEEE Transactions on Neural Networks 17

and the surprising structure of vortices

Define instead the imaginary.. potential, magnetic field, lattice…) Dirac-BdG Hamiltonian:. with small, and matrix

受資助機構企業管治指引

Internal Control and Management Practices in Non-Profit Organisations Northern India Regional Council of the Institute of Chartered Accounts of India Terrance S. Demczur