alpha-2-adrenergic receptors include 3 highly homologous subtypes: alpha, alpha, and alpha. these receptors have a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system. studies in mice revealed that both the alpha and alpha subtypes were required for normal presynaptic control of transmitter release from sympathetic nerves in the heart and from central noradrenergic neurons; the alpha subtype inhibited transmitter release at high stimulation frequencies, whereas the alpha subtype modulated neurotransmission at lower levels of nerve activity.