Reassessment of α1-adrenoceptor mechanism in artery contraction: role of ATP and pannexin channels

Project Details

The traditional mechanism of sympathetic nerve release of noradrenaline to activate post-junctional a1-adrenoceptors and subsequent vasoconstriction has been challenged. The new hypothesis is that noradrenaline-activated α1-adrenoceptors post-junctionally activate membrane pannexin-1 channels that open to release smooth muscle intracellular ATP that then back-activates in an autacoid manner P2X receptors that cause the contraction of the blood vessel. The evidence to support this pannexin-1 mechanism relied on a non-specific agent use to treat malaria, mefloquine. We have established that mefloquine is a non-specific antagonist with a multitude of actions, that a specific ATP P2X receptor antagonist has no effect on the α1-adrenoceptor mechanism and, therefore, the role for pannexin channels is without foundation in the α1-adrenoceptor cascade of vasoconstriction. The take home message here is that the investigator must be held to account when using pharmacological agents as tools to unravel mechanism that the agent used at that concentration has a unique action. Mefloquine has a wide range of properties at the concentration necessary to block α1-adrenoceptor actions that precluded a unique pannexin-1 antagonism.

Researchers

Associate Professor Christine E. Wright, BSc Hons, PhD, Laboratory Head

Mr Mark Ross-Smith, BSc Hons, Senior Research Assistant

Mr Ashenafi Betrie, BSc, MSc (Ethiopia), PhD candidate

Funding

Miscellaneous Grants

Research Publications

  • Angus JA, Betrie AH, Wright CE. Pannexin-1 channels do not regulate α1-adrenoceptor-mediated vasoconstriction in resistance arteries. Eur J Pharmacol 2015; 750: 43-51.
  • Angus JA, Wright CE. ATP is not involved in a1-adrenoceptor-mediated vasoconstriction in resistance arteries. Eur J Pharmacol 2015; 769: 162-166.

Research Group

Wright laboratory: Cardiovascular Therapeutics Unit


School Research Themes

Cardio-Respiratory



Key Contact

For further information about this research, please contact the research group leader.

Department / Centre

Pharmacology and Therapeutics

Unit / Centre

Wright laboratory: Cardiovascular Therapeutics Unit