Which presynaptic receptor inhibits release of norepinephrine?

• A. Alpha 1
• B. Beta 2
• C. Alpha 2
• D. Muscarinic

Answer: (C)

The main idea is how presynaptic autoreceptors control transmitter release. The receptor that dampens norepinephrine release is the alpha-2 adrenergic receptor on the presynaptic terminal. When this receptor is activated, it couples to a Gi protein, which lowers cAMP and inhibits voltage-gated calcium channels. With less calcium entering the neuron, fewer vesicles fuse, and less norepinephrine is released. This negative feedback helps keep sympathetic signaling in check. Clinically, drugs that activate alpha-2 receptors reduce NE release, illustrating this mechanism. Other receptors listed don’t serve this presynaptic inhibitory role: alpha-1 is typically postsynaptic and mediates vasoconstriction, beta-2 is a Gs receptor generally linked to different postsynaptic effects, and muscarinic receptors respond to acetylcholine, not norepinephrine.