CB1 receptor antagonist SR141716A increases capsaicin-evoked release of Substance P from the adult mouse spinal cord

被引:39
作者
Lever, IJ [1 ]
Malcangio, M [1 ]
机构
[1] Kings Coll London, Guys Kings & St Thomas Sch Biomed Sci, Neurosci Res Ctr, London SE1 1UL, England
关键词
cannabinoids; Substance P; spinal cord; sensory neurones;
D O I
10.1038/sj.bjp.0704506
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Cannabinoids have an antinociceptive action in many pain models. We have investigated a possible modulatory role for Type 1 Cannabinoid receptors (CB1) on the release of excitatory transmitter Substance P from the adult mouse spinal cord after stimulation of nociceptor terminals by capsaicin. Capsaicin (0.1 - 10 muM) was applied to superfused cord sections and evoked a dose dependent release of SP above basal outflow of (23.36+/-2.96 fmol 8 ml(-1)). Maximum evoked SP release was obtained with 5 muM Capsaicin (262.4+/-20.8 fmol 8 ml(-1)). Higher capsaicin concentrations (50 - 100 mum) evoked less SP release. Superfusion of CB1 antagonist SR141716A (5 muM) increased evoked SP release with capsaicin (0.1-10 muM) and reversed the reducing effect of high dose capsaicin (100 km). Antagonism of CB1 receptors in the spinal cord during capsaicin stimulation, is evidence of tonic CB1 activity inhibiting the release of excitatory transmitters after activation of nociceptive neurones and is also indicative of endocannabinoid production during noxious stimulation.
引用
收藏
页码:21 / 24
页数:4
相关论文
共 20 条
[1]   Cannabinoid 1 receptors are expressed in nociceptive primary sensory neurons [J].
Ahluwalia, J ;
Urban, L ;
Capogna, M ;
Bevan, S ;
Nagy, I .
NEUROSCIENCE, 2000, 100 (04) :685-688
[2]  
BEVAN S, 1990, TRENDS PHARMACOL SCI, V11, P330
[3]   The capsaicin receptor: a heat-activated ion channel in the pain pathway [J].
Caterina, MJ ;
Schumacher, MA ;
Tominaga, M ;
Rosen, TA ;
Levine, JD ;
Julius, D .
NATURE, 1997, 389 (6653) :816-824
[4]   Levels, metabolism, and pharmacological activity of anandamide in CB1 cannabinoid receptor knockout mice:: Evidence for non-CB1, non-CB2 receptor-mediated actions of anandamide in mouse brain [J].
Di Marzo, V ;
Breivogel, CS ;
Tao, Q ;
Bridgen, DT ;
Razdan, RK ;
Zimmer, AM ;
Zimmer, A ;
Martin, BR .
JOURNAL OF NEUROCHEMISTRY, 2000, 75 (06) :2434-2444
[5]   Hypolocomotor effects in rats of capsaicin and two long chain capsaicin homologues [J].
Di Marzo, V ;
Lastres-Becker, I ;
Bisogno, T ;
De Petrocellis, L ;
Milone, A ;
Davis, JB ;
Fernandez-Ruiz, JJ .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2001, 420 (2-3) :123-131
[6]   FORMATION AND INACTIVATION OF ENDOGENOUS CANNABINOID ANANDAMIDE IN CENTRAL NEURONS [J].
DIMARZO, V ;
FONTANA, A ;
CADAS, H ;
SCHINELLI, S ;
CIMINO, G ;
SCHWARTZ, JC ;
PIOMELLI, D .
NATURE, 1994, 372 (6507) :686-691
[7]   Cannabinoid CB1 receptor expression in rat spinal cord [J].
Farquhar-Smith, WP ;
Egertová, M ;
Bradbury, EJ ;
McMahon, SB ;
Rice, ASC ;
Elphick, MR .
MOLECULAR AND CELLULAR NEUROSCIENCE, 2000, 15 (06) :510-521
[8]   Regulation of cannabinoid and mu opioid receptors in rat lumbar spinal cord following neonatal capsaicin treatment [J].
Hohmann, AG ;
Herkenham, M .
NEUROSCIENCE LETTERS, 1998, 252 (01) :13-16
[9]   Substance P:: a pioneer amongst neuropeptides [J].
Hökfelt, T ;
Pernow, B ;
Wahren, J .
JOURNAL OF INTERNAL MEDICINE, 2001, 249 (01) :27-40
[10]  
HOLZER P, 1991, PHARMACOL REV, V43, P143