Adrenaline: More than a century after its discovery and still a mystery

Abstract

Adrenaline, also known as epinephrine, is traditionally involved in the "fight-or-flight response" [1]. Adrenaline was discovered at the end of the nineteenth century and isolated at the beginning of the twentieth century [2]. The catecholamines adrenaline and noradrenaline are the major effectors of the adrenergic nervous system [3]. They are synthesized by enzymatic conversion of dopamine to noradrenaline by the action of dopamine-hydroxylase. Noradrenaline is stored in vesicles for release into the synaptic cleft of neurons after stimulation by adrenergic nervous impulse [4]. Noradrenaline can be converted to adrenaline by phenylethanolamine-N-methyltransferase (Pnmt), a cytoplasmic enzyme [3]. Adrenaline is mainly synthesized in adrenal medulla and released to the bloodstream; other tissues, such as the heart and blood vessels also have Pnmt and can synthesize adrenaline [5-7]. Adrenaline and noradrenaline interact with αand β-adrenergic receptors to mediate most cardiovascular effects of catecholamines [4]. Cardiac β-adrenergic receptors are mostly β 1 subtype, whose stimulation increases chronotropism and inotropism; most noncardiac receptors are β 2 [4]. The α-adrenergic receptors α 1 and α 2 are predominantly located in blood vessels. In peripheral and coronary arteries, the α 1adrenergic receptor mediates constriction, while the β 2-adrenergic receptor mediates dilation. In β 1 receptors, adrenaline and noradrenaline have a similar potency; in β 2 receptors, adrenaline is more potent than noradrenaline [5]. The α 1-agonist potency of noradrenaline is higher than that of adrenaline [4].