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Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Potently Dilates Middle Meningeal Arteries: Implications for Migraine

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Abstract

Migraine is a debilitating neurological disorder characterized by mild to severe headache that is often accompanied by aura and other neurological symptoms. Among proposed mechanisms, dilation of the dural vasculature especially the middle meningeal artery (MMA) has been implicated as one component underlying this disorder. Several regulatory peptides from trigeminal sensory and sphenopalatine postganglionic parasympathetic fibers innervating these vessels have been implicated in the process including pituitary adenylate cyclase-activating polypeptide (PACAP). Although PACAP has been well described as a potent dilator in many vascular beds, the effects of PACAP on the dural vasculature are unclear. In the current study, we examined the ability of PACAP to dilate MMAs that were isolated from rats and pressurized ex vivo. PACAP38 potently dilated pressurized MMAs with an EC50 of 1 pM. The PAC1 receptor antagonist, PACAP(6-38), abolished MMA dilation caused by picomolar concentrations of PACAP. In contrast, cerebellar arteries isolated from the brain surface were ~1,000-fold less sensitive to PACAP than MMAs. Although cerebellar arteries expressed transcripts for all three PACAP receptor subtypes (PAC1, VPAC1, and VPAC2 receptors) by RT-PCR analyses, MMA demonstrated only PAC1 and VPAC2 receptor expression. Further, multiple variants of the PAC1 receptor were identified in the MMA. The expression of PAC1 receptors and the high potency of PACAP to induce MMA vasodilation are consistent with their potential roles in the etiology of migraine.

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Acknowledgments

The authors wish to thank Mr. Kevin O'Connor for his assistance and acknowledge the University of Vermont Neuroscience COBRE molecular biology core facility. This work was supported by the Totman Medical Research Trust and National Institutes of Health Grants P01-HL-2095488, P20-RR-16435, and R01-HL-078983.

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No conflicts of interest, financial or otherwise, are declared by the authors.

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Authors and Affiliations

  1. Department of Pharmacology, University of Vermont, 89 Beaumont Avenue, Burlington, VT, 05405-0068, USA

    Arsalan U. Syed, Masayo Koide, Victor May & George C. Wellman

  2. Department of Neurological Sciences, University of Vermont College of Medicine, 149 Beaumont Avenue, Burlington, VT, 05405-0068, USA

    Karen M. Braas & Victor May

Authors
  1. Arsalan U. Syed
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  2. Masayo Koide
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  3. Karen M. Braas
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  4. Victor May
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  5. George C. Wellman
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Correspondence to George C. Wellman.

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Syed, A.U., Koide, M., Braas, K.M. et al. Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Potently Dilates Middle Meningeal Arteries: Implications for Migraine. J Mol Neurosci 48, 574–583 (2012). https://doi.org/10.1007/s12031-012-9851-0

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  • DOI: https://doi.org/10.1007/s12031-012-9851-0

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