TY - JOUR

T1 - Effect of K-ATP channel blocker glibenclamide on PACAP38-induced headache and hemodynamic

AU - Kokoti, Lili

AU - Al-Karagholi, Mohammad Al-Mahdi

AU - Elbahi, Fatima Azzahra

AU - Coskun, Hande

AU - Ghanizada, Hashmat

AU - Amin, Faisal Mohammad

AU - Ashina, Messoud

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Humans

KW - migraine

KW - glyburide

KW - pituitary adenylate cyclase activating polypeptide-38

KW - cranial arteries

KW - CYCLASE-ACTIVATING POLYPEPTIDE

KW - MIGRAINE-LIKE ATTACKS

KW - GENE-RELATED PEPTIDE

KW - ADENYLATE-CYCLASE

KW - TRANSCRANIAL DOPPLER

KW - POTASSIUM CHANNELS

KW - MESSENGER-RNA

KW - ARTERIES

KW - RECEPTORS

KW - PACAP38

U2 - 10.1177/03331024221080574

DO - 10.1177/03331024221080574

M3 - Journal article

C2 - 35301859

VL - 42

SP - 846

EP - 858

JO - Cephalalgia

JF - Cephalalgia

SN - 0800-1952

IS - 9

ER -