Stimulation of alpha-2 adrenergic receptors presynaptically at a sympathetic nerve terminal produces which effect?

• A Increased norepinephrine release via positive feedback
• B Increased cAMP, enhancing vesicular norepinephrine packaging
• C Decreased norepinephrine release via autoreceptor-mediated negative feedback ✓
• D Activation of IP3/DAG pathway, triggering exocytosis

Explanation

Presynaptic alpha-2 adrenergic receptors on sympathetic nerve terminals are autoreceptors: when activated by released norepinephrine, they inhibit further NE release via Gi protein coupling, reducing cAMP and decreasing Ca2+-dependent exocytosis. This provides short-loop negative feedback to limit excessive sympathetic activity. Postsynaptic alpha-2 receptors (e.g., in the CNS, vasculature) have different roles; central alpha-2 agonists like clonidine reduce sympathetic outflow by activating these inhibitory receptors in the brainstem.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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