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In addition, \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptors are pharmacological targets for the treatment of hypertension, sympathetic overactivity and glaucoma. \u03b1<jats:sub>2<\/jats:sub>\u2010Adrenoceptors are also targeted to induce sedation and analgesia in anaesthesia and intensive care. \u03b1<jats:sub>2<\/jats:sub>\u2010Adrenoceptors 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, \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptors were also identified in many non\u2010neuronal cell types of the body. Gene\u2010targeting in mice provided a comprehensive assignment of the physiological and pharmacological functions of these receptors to specific \u03b1<jats:sub>2A<\/jats:sub>\u2010, \u03b1<jats:sub>2B<\/jats:sub>\u2010 and \u03b1<jats:sub>2C<\/jats:sub>\u2010adrenoceptor subtypes. However, the specific cell types and signalling pathways involved in these subtype\u2010specific \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor functions were largely unexplored until recently. This review summarizes recent findings from transgenic mouse models, which were generated to define the role of \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptors in adrenergic neurons, that is, \u03b1<jats:sub>2<\/jats:sub>\u2010autoreceptors, versus \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptors in non\u2010adrenergic neurons, termed \u03b1<jats:sub>2<\/jats:sub>\u2010heteroreceptors. \u03b1<jats:sub>2<\/jats:sub>\u2010Autoreceptors 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 \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor agonist drugs essentially require \u03b1<jats:sub>2<\/jats:sub>\u2010heteroreceptors in non\u2010adrenergic neurons, including analgesia, sedation, hypothermia and anaesthetic\u2010sparing as well as bradycardia and hypotension. Thus a clear picture has emerged of the significance of auto\u2010 versus heteroreceptors in mediating the physiological functions of \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptors and the pharmacological functions of \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor agonist drugs respectively.<\/jats:p>","DOI":"10.1111\/j.1476-5381.2011.01533.x","type":"journal-article","created":{"date-parts":[[2011,6,10]],"date-time":"2011-06-10T04:44:53Z","timestamp":1307681093000},"page":"90-102","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":96,"title":["Are the pharmacology and physiology of \u03b1<sub>2<\/sub>adrenoceptors determined by \u03b1<sub>2<\/sub>\u2010heteroreceptors and autoreceptors 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