An Extract (THC-002) of Ba-Wei-Die-Huang-Wan Inhibits Expression of Tachykinins, and P2X3 and TRPV1 Receptors, and Inhibits ATP-Induced Detrusor Overactivity in Spontaneously Hypertensive Rats

被引:20
作者
Imamura, Tetsuya [1 ]
Ishizuka, Osamu [1 ]
Zhong, Chen [1 ]
Ogawa, Teruyuki [1 ]
Nakayama, Tsuyoshi [1 ]
Kurizaki, Yoshiki [1 ]
Tanabe, Tomoaki [1 ]
Nishizawa, Osamu [1 ]
Andersson, Karl-Erik [2 ]
机构
[1] Shinshu Univ, Sch Med, Dept Urol, Matsumoto, Nagano 3908621, Japan
[2] Wake Forest Univ, Sch Med, Wake Forest Inst Regenerat Med, Winston Salem, NC 27109 USA
关键词
detrusor overactivity; P2X3; receptor; SHR; tachykinins; THC-002; TRPV1; urinary bladder; URINARY-BLADDER; MICTURITION REFLEX; ACTIVATION;
D O I
10.1002/nau.20702
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Aims: To investigate possible mechanisms of action of THC-002 (HARNCARE(R)), a galenical produced from the traditional Chinese herbal mixture Ba-Wei-Die-Huang-Wan, which has been reported to improve lower urinary tract symptoms (LUTS) in patients. Methods: Forty-five female SHRs were randomly separated into three groups. Two groups were given 20 ml physiological saline solution (PSS) per kg-body weight orally daily for 1 week. An hour after the administration of PSS, one of the groups received 20 mg THC-002 per kg body weight, and the other a similar volume of THC-002-free saline. The third group received no treatments. The bladders were analyzed by real time RT-PCR (n = 6) and immunohistochemistry (n = 3) for the expression of tachykinins and P2X3 and TRPV1 receptors. Cystometric investigation (n = 6) was conducted after intravesical instillation of saline followed by 5 mg/ml ATP solution. Results: Treatment with PSS caused and upregulation of tachykinins and P2X3 and TRPV1 receptors, which was prevented in the group treated with THC-002. In the normal (non-treated) and non-THC-002-treated SHRs, instillation of the ATP solution decreased voiding interval, micturition volume, and bladder capacity compared to the instillation of saline. However, in the THC-002-treated SHRs, ATP instillation had no effect. Conclusions: In SHRs, THC-002 reduced the bladder expression of tachykinins and P2X3 and TRPV1 receptors, and inhibited ATP-induced detrusor overactivity. These effects may explain part of its beneficial effects on LUTS. Neurourol. Urodynarn. 28:529-534, 2009. (C) 2009 Wiley-Liss, Inc.
引用
收藏
页码:529 / 534
页数:6
相关论文
共 18 条
[1]   Bladder activation: Afferent mechanisms [J].
Andersson, KE .
UROLOGY, 2002, 59 (5A) :43-50
[2]   Capsaicin receptor TRPV1 in urothelium of neurogenic human bladders and effect of intravesical resiniferatoxin [J].
Apostolidis, A ;
Brady, CM ;
Yiangou, Y ;
Davis, J ;
Fowler, CJ ;
Anand, P .
UROLOGY, 2005, 65 (02) :400-405
[3]   P2X3-immunoreactive nerve fibres in neurogenic detrusor overactivity and the effect of intravesical resiniferatoxin [J].
Brady, CM ;
Apostolidis, A ;
Yiangou, Y ;
Baecker, PA ;
Ford, AP ;
Freeman, A ;
Jacques, TS ;
Fowler, CJ ;
Anand, P .
EUROPEAN UROLOGY, 2004, 46 (02) :247-253
[4]   Identification of a tachykinin NK2 receptor splice variant and its expression in human and rat tissues [J].
Candenas, ML ;
Cintado, CG ;
Pennefather, JN ;
Pereda, MT ;
Loizaga, JM ;
Maggi, CA ;
Pinto, FM .
LIFE SCIENCES, 2002, 72 (03) :269-277
[5]   Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice [J].
Cockayne, DA ;
Hamilton, SG ;
Zhu, QM ;
Dunn, PM ;
Zhong, Y ;
Novakovic, S ;
Malmberg, AB ;
Cain, G ;
Berson, A ;
Kassotakis, L ;
Hedley, L ;
Lachnit, WG ;
Burnstock, G ;
McMahon, SB ;
Ford, APDW .
NATURE, 2000, 407 (6807) :1011-1015
[6]   Gosha-jinki-gan Reduces Transmitter Proteins and Sensory Receptors Associated with C Fiber Activation Induced by Acetic Acid in Rat Urinary Bladder [J].
Imamura, Tetsuya ;
Ishizuka, Osamu ;
Aizawa, Naoki ;
Zhong, Chen ;
Ogawa, Teruyuki ;
Nakayama, Tsuyoshi ;
Tanabe, Tomoaki ;
Nishizawa, Osamu .
NEUROUROLOGY AND URODYNAMICS, 2008, 27 (08) :832-837
[7]   TACHYKININ EFFECTS ON BLADDER ACTIVITY IN CONSCIOUS NORMAL RATS [J].
ISHIZUKA, O ;
MATTIASSON, A ;
ANDERSSON, KE .
JOURNAL OF UROLOGY, 1995, 154 (01) :257-261
[8]  
Ishizuka O, 2006, VOIDING DISORDERS DI, V14, P95
[9]   Tachykinins as modulators of the micturition reflex in the central and peripheral nervous system [J].
Lecci, A ;
Maggi, CA .
REGULATORY PEPTIDES, 2001, 101 (1-3) :1-18
[10]   INCREASE IN PRESUMPTIVE SENSORY NERVES OF THE URINARY-BLADDER IN IDIOPATHIC DETRUSOR INSTABILITY [J].
MOORE, KH ;
GILPIN, SA ;
DIXON, JS ;
RICHMOND, DH ;
SUTHERST, JR .
BRITISH JOURNAL OF UROLOGY, 1992, 70 (04) :370-372