Methamphetamine induces the release of endothelin

• Published in: Journal of neuroscience research 2016-02, Vol.94 (2), p.170-178
• Main Authors: Seo, Jeong-Woo, Jones, Susan M., Hostetter, Trisha A., Iliff, Jeffrey J., West, G. Alexander
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Arteries - drug effects; Brain - cytology; Cell Line, Transformed; Cell Survival - drug effects; Central Nervous System Stimulants - pharmacology; Dose-Response Relationship, Drug; endothelial cells; endothelin; Endothelin-1 - antagonists & inhibitors; Endothelin-1 - genetics; Endothelin-1 - metabolism; Endothelium - drug effects; Enzyme-Linked Immunosorbent Assay; isolated intracerebral arterioles; methamphetamine; Methamphetamine - pharmacology; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type III - metabolism; Oligopeptides - pharmacology; RNA, Messenger - metabolism; Time Factors; vasoconstriction; Vasoconstriction - drug effects
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.23697

Methamphetamine is a potent psychostimulant drug of abuse that increases release and blocks reuptake of dopamine, producing intense euphoria, factors that may contribute to its widespread abuse. It also produces severe neurotoxicity resulting from oxidative stress, DNA damage, blood–brain barrier disruption, microgliosis, and mitochondrial dysfunction. Intracerebral hemorrhagic and ischemic stroke have been reported after intravenous and oral abuse of methamphetamine. Several studies have shown that methamphetamine causes vasoconstriction of vessels. This study investigates the effect of methamphetamine on endothelin‐1 (ET‐1) release in mouse brain endothelial cells by ELISA. ET‐1 transcription as well as endothelial nitric oxide synthase (eNOS) activation and transcription were measured following methamphetamine treatment. We also examine the effect of methamphetamine on isolated cerebral arteriolar vessels from C57BL/6 mice. Penetrating middle cerebral arterioles were cannulated at both ends with a micropipette system. Methamphetamine was applied extraluminally, and the vascular response was investigated. Methamphetamine treatment of mouse brain endothelial cells resulted in ET‐1 release and a transient increase in ET‐1 message. The activity and transcription of eNOS were only slightly enhanced after 24 hr of treatment with methamphetamine. In addition, methamphetamine caused significant vasoconstriction of isolated mouse intracerebral arterioles. The vasoconstrictive effect of methamphetamine was attenuated by coapplication of the endothelin receptor antagonist PD145065. These findings suggest that vasoconstriction induced by methamphetamine is mediated through the endothelin receptor and may involve an endothelin‐dependent pathway. © 2015 Wiley Periodicals, Inc. This study demonstrates that methamphetamine (MA) stimulates the release of endothelin (ET‐1) from cultured endothelial cells. In isolated arterioles, vasoconstriction induced by MA is blocked by ET‐1 receptor antagonist, suggesting that the vasoconstrictive effect of MA is mediated through the release of ET‐1.