Physiological and pharmacological aspects of adrenergic receptor classification

The questions raised are: what is the physiological or pharmacological basis for the differentiation into β₁- and β₂-, and α₁- and α₂-adrenergic receptors?; and do the neurotransmitter norepinephrine and the hormone epinephrine differ in their receptors? On the basis of a preference of β₂- and α₂-adrenergic receptors for epinephrine, the hormone, and of β₁- and α₁-receptors for norepinephrine, the neurotransmitter, it was postulated that the α₂- and β₂-receptors are predominantly epinephrinergic in nature and located extrajunctionally and presynaptically whereas the α₁- and β₁-receptors are predominantly norepinephrinergic in nature and located postsynaptically in the sympathetic terminal junction. The α₂- and β₂-character of the presynaptic receptors matches that of the corresponding extrajunctional receptors. This indicates that a circulating catecholamine, namely epinephrine, is involved in the regulation of adrenergic transmitter release.