Question

There are two main types of adrenergic receptors: the alpha and beta adrenoceptors. Noradrenaline shows slight selectivitty for the alpha receptor, whereas isoprenaline shows selectivity for the beta adrenoceptor. Adrenaline shows no selectivity and binds equally well to both the alpha and beta forms of the adrenoceptors. Draw the chemical structures for noradrenaline, isoprenaline, and adrenaline. suggest an explanation for these differencse in selectivity relative to the binding site of each receptor.

Answer 1

Adrenaline shows no selectivity and binds equally well to both the alpha and beta forms of the adrenoceptors located at the "presynaptic nerves & smooth muscle", heart and muscle tissue (bet-1 & beta-2 receptrs loacted).

All the above three molecules (Adrenaline, NorAdrenaline, isoprenaline) can bind to 7-transmembrane (TM) G-protein coupled receptors i.e. adrenergic receptors

Adrenaline has three catechol-hydroxyl groups, another OH group attached to side chain & a tertiary methyl group that makes to attach with TM - 5 ser204 & ser208 and TM-6 Phe290 & Asn293, AH (CH3) is going to react with TM-3Asp113 (as shown in the above figure) . So that adrenaline can bind to all adrenergic receptors nonselectively. Noradrenaline can react with only alpha1- & alpha-2 receptors because of the lack of methyl group to react with TM-3 Asn whereas isoprenaline is going to show selectivity to beta-adrenergic G-protein coupled receptors due to presence of saturated "ammonium position in its side chain" and absence of stereo rotated (optically active) OH group on its side chain.