Cannabinoid receptor‐independent inhibition by cannabinoid agonists of the peripheral 5‐HT3 receptor‐mediated von Bezold–Jarisch reflex
Cannabinoid receptor‐independent inhibition by cannabinoid agonists of the peripheral 5‐HT3 receptor‐mediated von Bezold–Jarisch reflex
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大麻素激动剂对外周 5-HT3 受体介导的 von Bezold-Jarisch 反射的大麻素受体独立抑制
DOI：
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发表时间：
2003
影响因子：
7.3
通讯作者：
B. Malinowska
中科院分区：
文献类型：
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作者：
G. Godlewski;M. Göthert;B. Malinowska
基于大麻素在体外抑制人和大鼠5-HT 3受体功能的先前发现，我们研究了大麻素受体激动剂是否也在体内调节大鼠外周5-HT 3受体在心肺传入C纤维末端的活性。在氨基甲酸乙酯麻醉大鼠中，静脉内（i. v.）与CB 1受体拮抗剂SR 141716 A（3 μmol kg−1）和β1/β2肾上腺素受体拮抗剂普萘洛尔（0.3-0.4 μmol kg−1），推注5-羟色胺5-HT 3受体激动剂苯基双胍（3-10 μg kg−1，i. v.）或香草素VR 1受体激动剂辣椒素（3-10 μg kg-1，i. v.）导致心率和平均动脉血压立即下降（von Bezold-Jorch反射）。大麻素受体激动剂CP 55，940（0.1-1 μmol kg−1，i. v.）和WIN 55，212 - 2（0.1-3 μmol kg−1，i.v.）注射后20分钟，但不是由后者的无活性S-（-）对映体，WIN 55，212 - 3（1 μmol kg−1，i. v.）。抑制在30分钟内是可逆的。大麻素受体激动剂的最高剂量的抑制程度达约50%。两种大麻素受体激动剂均未能影响辣椒素诱发的心动过缓。总之，我们的研究结果表明，大麻素受体激动剂通过抑制大鼠体内外周5-羟色胺5-HT 3受体来调节von Bezold-Jorch反射。大麻素受体激动剂的类似机制可能被认为参与其他5-羟色胺5-HT 3受体介导的反应。
On the basis of previous findings that cannabinoids inhibit the function of human and rat 5‐HT3 receptors in vitro, we investigated whether cannabinoid receptor agonists also modulate the activity of the rat peripheral 5‐HT3 receptors on the terminals of cardiopulmonary afferent C‐fibres in vivo. In urethane‐anaesthetized rats, pre‐treated intravenously (i.v.) with the CB1 receptor antagonist SR 141716A (3 μmol kg−1) and with the β1/β2 adrenoceptor antagonist propranolol (0.3–0.4 μmol kg−1), bolus injection of the serotonin 5‐HT3 receptor agonist phenylbiguanide (3–10 μg kg−1, i.v.) or the vanilloid VR1 receptor agonist capsaicin (3–10 μg kg−1, i.v.) caused an immediate decrease in heart rate and mean arterial blood pressure (the von Bezold–Jarisch reflex). The phenylbiguanide‐induced bradycardia was dose‐dependently attenuated by the cannabinoid receptor agonists CP 55,940 (0.1–1 μmol kg−1, i.v.) and WIN 55,212‐2 (0.1–3 μmol kg−1, i.v.) 20 min after injection, but not by the inactive S‐(−)enantiomer of the latter, WIN 55,212‐3 (1 μmol kg−1, i.v.). The inhibition was reversible within 30 min. The extent of inhibition by the highest doses of cannabinoid receptor agonists amounted to about 50%. Both cannabinoid receptor agonists failed to affect the capsaicin‐evoked bradycardia. In conclusion, our results demonstrate that cannabinoid receptor agonists modulate the von Bezold–Jarisch reflex by inhibiting peripheral serotonin 5‐HT3 receptors in rats in vivo. An analogous mechanism of cannabinoid receptor agonists may be assumed to be involved in other serotonin 5‐HT3 receptor‐mediated responses.
辣椒素消除麻醉大鼠中辣椒素诱导的肺化学反射。
DOI：
10.1152/jappl.1994.76.5.1848
发表时间：
1994
期刊：
Journal of applied physiology (Bethesda, Md. : 1985)
影响因子：
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作者：
Lee,LY;Lundberg,JM
通讯作者：
Lundberg,JM
新型拮抗剂表明 CB1 大麻素受体与 anandamide 的降血压作用有关。
影响因子：
5
作者：
Varga,K;Lake,K;Martin,BR;Kunos,G
通讯作者：
Kunos,G