Excitatory transmission to the circular muscle of the guinea-pig ileum:: evidence for the involvement of cannabinoid CB1 receptors
Excitatory transmission to the circular muscle of the guinea-pig ileum:: evidence for the involvement of cannabinoid CB1 receptors
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DOI：
10.1038/sj.bjp.0701964
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发表时间：
1998-08-01
影响因子：
7.3
通讯作者：
Capasso, F
中科院分区：
文献类型：
--
作者：
Izzo, AA;Mascolo, N;Capasso, F
1.研究了大麻素药物对豚鼠回肠环形平滑肌的胆碱能和非肾上腺素能非胆碱能（NANC）收缩反应的影响，所述收缩反应由电保持刺激（EFS）引起。2大麻素受体激动剂WIN 55，212-2（1-1000 nM）和假定的内源性配体花生四烯酸酰胺（0.1-100 μ M）对胆碱能（9-57%和1-51%抑制）和NANC（9-55%和2-57%抑制）收缩反应均产生浓度依赖性抑制。WIN 55，212 -2和大麻素不能改变外源性乙酰胆碱或P.3物质产生的收缩，Apamin（30 nM）是一种Ca 2+激活的K+通道阻滞剂，可降低WIN 55，212 -2对胆碱能收缩反应的抑制作用，但不能降低NANC收缩反应。N-硝基-L-精氨酸甲酯（100 μ M），一氧化氮合酶抑制剂，或纳洛酮（1 μ M），阿片受体拮抗剂，没有改变WIN 55，212 -2对胆碱能和NANC收缩的抑制作用。大麻素CBI受体拮抗剂SR 141716 A竞争性拮抗212-2和大麻素对胆碱能和NANC收缩反应的抑制作用（10-1000 nM）。5在没有其他药物的情况下，SR 141716 A（1-1000 nhl）增强的胆碱能（1-45%增加）和NANC（增加2-38%）电刺激引起的收缩反应，但并不改变乙酰胆碱或P物质产生的收缩。6结论是，连接前大麻素CB 1受体的激活产生抑制，豚鼠环形肌中的胆碱能和NANC兴奋性反应。胆碱能（但非NANC）传递的抑制涉及apamin敏感性K+通道的激活。此外，内源性大麻素配体可以抑制豚鼠回肠环行肌中的胆碱能和NANC传递。
1. The effect of cannabinoid drugs has been investigated on cholinergic and non-adrenergic noncholinergic (NANC) contractile responses to the circular smooth muscle of guinea-pig ileum elicited by electrical held stimulation (EFS).2 The cannabinoid receptor agonist WIN 55,212-2 (1-1000 nM) and the putative endogenous ligand anandamide (0.1-100 mu M) both produced a concentration-dependent inhibition of the cholinergic (9-57% and 1-51% inhibition) and NANC (9-55% and 2-57% inhibition) contractile responses. WIN 55,212-2 and anandamide did not modify the contractions produced by exogenous acetylcholine or substance P.3 Apamin (30 nM), a blocker of Ca2+-activated K+ channels, reduced the inhibitory effect of WIN 55,212-2 on cholinergic, but not NANC, contractile response. N-G-nitro-L-arginine methyl ester (100 mu M), an inhibitor of nitric oxide synthase, or naloxone (1 mu M), an opioid receptors antagonist, did not modify the inhibitory effect of WIN 55,212-2 on both cholinergic and NANC contractions.4 The inhibitory effects of WIN 55,212-2 and anandamide on both cholinergic and NANC contractile response was competitively antagonized by the cannabinoid CBI receptor antagonist SR 141716A (10-1000 nM).5 In absence of other drugs, SR 141716A (1-1000 nhl) enhanced cholinergic (1-45% increase) and NANC (2-38% increase) contractile responses elicited by electrical stimulation, but did not modify the contractions produced by acetylcholine or substance P.6 It is concluded that activation of prejunctional cannabinoid CB1 receptors produces inhibition of cholinergic and NANC excitatory responses in the guinea-pig circular muscle. The inhibition of cholinergic (but not NANC) transmission involves activation of apamin-sensitive K+ channels. In addition, an endogenous cannabinoid ligand could inhibit cholinergic and NANC transmission in the guinea-pig ileal circular muscle.