Alpha-2 adrenoceptors on presynaptic noradrenergic nerve terminals serve as autoreceptors. Activation of these receptors by an agonist such as clonidine leads to which of the following primary intracellular consequences?

• A Increased cAMP via Gs protein stimulation
• B Activation of phospholipase C leading to IP3 generation
• C Decreased cAMP via Gi protein inhibition of adenylyl cyclase ✓
• D Increased intracellular calcium via voltage-gated channels

Explanation

Alpha-2 receptors couple to Gi proteins, which inhibit adenylyl cyclase, thereby reducing intracellular cAMP. In presynaptic terminals, this reduction in cAMP decreases vesicular docking and norepinephrine release, producing a negative feedback effect. This mechanism underlies clonidine's central antihypertensive action by reducing sympathetic outflow. Alpha-1 receptors (not alpha-2) signal via Gq/phospholipase C and IP3.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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