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Effect of pituitary adenylate cyclase-activating polypeptide-27 on cerebral hemodynamics in healthy volunteers: A 3T MRI study

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  1. Procholecystokinin expression and processing in cardiac myocytes

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  2. Serum proatrial natriuretic peptide concentrations during oral glucose-induced acute hyperinsulinemia in lean and obese men

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  1. Eptinezumab in episodic migraine: A randomized, double-blind, placebo-controlled study (PROMISE-1)

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  2. Higher physiological vulnerability to hypoxic exposure with advancing age in the human brain

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  3. Investigation of sumatriptan and ketorolac trometamol in the human experimental model of headache

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  4. PACAP27 induces migraine-like attacks in migraine patients

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  5. Reply: Hyperpolarization through ATP-sensitive potassium channels; relevance to migraine pathology

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Pituitary adenylate cyclase-activating polypeptide (PACAP) has emerged as an important signaling peptide in migraine pathogenesis. Recently, we have shown that the less-abundant PACAP isoform, PACAP27, induced migraine and headache in patients equipotently to PACAP38. The present study examined the effect of PACAP27 on cerebral hemodynamics in healthy volunteers using high resolution magnetic resonance angiography (MRA). Eighteen healthy volunteers received infusion of PACAP27 (10 pmol/kg/min) or placebo over 20 min and were scanned repeatedly in fixed intervals for 5 h in a double-blind, randomized, placebo-controlled study. The circumference of extra-intracerebral arteries was measured and compared with PACAP38 data. We found significant dilation of middle meningeal artery (MMA) (p = 0.019), superficial temporal artery (p = 0.001) and external carotid artery (p = 0.039) after PACAP27 infusion compared to placebo. Whereas the middle cerebral artery (MCA) (p = 0.011) and internal carotid artery (ICA) (pICAcervical = 0.015, pICAcerebral = 0.019) were constricted. No effects on basilar artery (p = 0.708) and cavernous portion of ICA were found. Post hoc analyses revealed significant larger area under the curve for MMA after PACAP38 compared to PACAP27 (p = 0.033). We also found that PACAP27 induced headache in nine out of twelve (75%) volunteers and one (17%) after placebo. In conclusion, PACAP27 induced headache and dilated extracerebral arteries (>5 h) and slightly constricted MCA in healthy volunteers. Post hoc analysis of PACAP38 data compared with PACAP27 showed that PACAP isoforms dilates MMA with significantly different magnitude.

Original languageEnglish
JournalPeptides
Volume121
Pages (from-to)170134
ISSN0196-9781
DOIs
Publication statusPublished - Nov 2019

ID: 58653349