Effect of KATP channel blocker glibenclamide on PACAP38-induced headache and hemodynamic
Effect of KATP channel blocker glibenclamide on PACAP38-induced headache and hemodynamic
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DOI：
10.1177/03331024221080574
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发表时间：
2022-03-18
期刊：
影响因子：
4.9
通讯作者：
Ashina, Messoud
中科院分区：
文献类型：
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作者：
Kokoti, Lili;Al-Karagholi, Mohammad Al-Mahdi;Ashina, Messoud
目的研究非选择性三磷酸腺苷(K-ATP)通道阻滞剂格列本脲是否能减轻垂体腺苷环化酶激活多肽-38(PACAP38)引起的健康志愿者头痛和血管病变。方法采用双盲、随机、安慰剂对照、交叉试验设计，22名健康受试者先静脉滴注10 mg/kg/min的垂体腺苷环化酶激活多肽-38，20min后再口服格列本脲10 mg或安慰剂。主要终点是格列本脲和安慰剂在头痛发生率(0-12小时)上的差异。次要终点的头痛强度评分、大脑中动脉血流速度(V-ean MCA)、颞浅动脉内径、桡动脉内径、心率、平均动脉压和面部皮肤血流量的曲线下面积在两个研究日之间存在差异。结果20名受试者完成研究。我们发现优降糖(19/20，95%)与安慰剂(18/20，90%)相比，垂体腺苷环化酶激活多肽-38所致头痛的发生率没有差异(P=0.698)。头痛强度、大脑中动脉血流速度、颞浅动脉内径、桡动脉内径、面部皮肤血流量、心率和平均动脉压在垂体腺苷环化酶激活多肽-38-优降糖日与垂体腺苷环化酶激活多肽-38-安慰剂日相比差异无统计学意义(P>；0.05)。结论应用5‘-三磷酸敏感K+通道阻断剂格列本脲治疗后，并不能减轻垂体腺苷环化酶激活多肽38引起的头痛和血流动力学改变。我们认为，垂体腺苷环化酶激活多肽-38触发的信号通路可能是通过5‘-三磷酸敏感性钾通道的磺脲受体亚基亚基和其他类型的钾通道来介导的。
Objective To determine whether glibenclamide, a non-selective adenosine 5 '-triphosphate-sensitive K+ (K-ATP) channel blocker, attenuates pituitary adenylate cyclase-activating polypeptide-38 (PACAP38)-induced headache and vascular changes in healthy volunteers. Methods In a double-blind, randomized, placebo controlled and crossover design, 22 healthy volunteers were assigned to receive an intravenous infusion of 10 picomole/kg/min pituitary adenylate cyclase-activating polypeptide-38 over 20 minutes followed by oral administration of 10 mg glibenclamide or placebo. The primary endpoint was the difference in incidence of headache (0-12 hours) between glibenclamide and placebo. The secondary endpoints were a difference in area under the curve for headache intensity scores, middle cerebral artery velocity (V-meanMCA), superficial temporal artery diameter, radial artery diameter, heart rate, mean arterial blood pressure and facial skin blood flow between the two study days. Results Twenty participants completed the study. We found no difference in the incidence of pituitary adenylate cyclase-activating polypeptide-38-induced headache after glibenclamide (19/20, 95%) compared to placebo (18/20, 90%) (P = 0.698). The area under the curve for headache intensity, middle cerebral artery velocity, superficial temporal artery diameter, radial artery diameter, facial skin blood flow, heart rate and mean arterial blood pressure did not differ between pituitary adenylate cyclase-activating polypeptide-38-glibenclamide day compared to pituitary adenylate cyclase-activating polypeptide-38-placebo day (P > 0.05). Conclusions Posttreatment with 5 '-triphosphate-sensitive K+ channel inhibitor glibenclamide did not attenuate pituitary adenylate cyclase-activating polypeptide-38-induced headache and hemodynamic changes in healthy volunteers. We suggest that pituitary adenylate cyclase-activating polypeptide-38-triggered signaling pathway could be mediated by specific isoforms of sulfonylurea receptor subunits of 5 '-triphosphate-sensitive K+ channels and other types of potassium channels.