Article date: January 2012
By: Ralf Gilsbach, Lutz Hein in Volume 165, Issue 1, pages 90-102
α2‐Adrenoceptors are important mediators of physiological responses to the endogenous catecholamines noradrenaline and adrenaline. In addition, α2‐adrenoceptors are pharmacological targets for the treatment of hypertension, sympathetic overactivity and glaucoma. α2‐Adrenoceptors are also targeted to induce sedation and analgesia in anaesthesia and intensive care. α2‐Adrenoceptors were first described as presynaptic receptors inhibiting the release of various transmitters from neurons in the central and peripheral nervous systems. In addition to these presynaptic neuronal receptors, α2‐adrenoceptors were also identified in many non‐neuronal cell types of the body. Gene‐targeting in mice provided a comprehensive assignment of the physiological and pharmacological functions of these receptors to specific α2A‐, α2B‐ and α2C‐adrenoceptor subtypes. However, the specific cell types and signalling pathways involved in these subtype‐specific α2‐adrenoceptor functions were largely unexplored until recently. This review summarizes recent findings from transgenic mouse models, which were generated to define the role of α2‐adrenoceptors in adrenergic neurons, that is, α2‐autoreceptors, versus α2‐adrenoceptors in non‐adrenergic neurons, termed α2‐heteroreceptors. α2‐Autoreceptors are primarily required to limit release of noradrenaline from sympathetic nerves and adrenaline from adrenal chromaffin cells at rest. These receptors are desensitized upon chronic activation as it may for instance occur due to enhanced sympathetic activity during chronic heart failure. In contrast, pharmacological effects of acutely administered α2‐adrenoceptor agonist drugs essentially require α2‐heteroreceptors in non‐adrenergic neurons, including analgesia, sedation, hypothermia and anaesthetic‐sparing as well as bradycardia and hypotension. Thus a clear picture has emerged of the significance of auto‐ versus heteroreceptors in mediating the physiological functions of α2‐adrenoceptors and the pharmacological functions of α2‐adrenoceptor agonist drugs respectively.
DOI: 10.1111/j.1476-5381.2011.01533.x
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