Prolactin secretion is tonically inhibited by dopamine from the tuberoinfundibular pathway. Which receptor subtype on lactotroph cells mediates this inhibition, and what is the principal second messenger mechanism?
- A D2 receptor; couples to Gαi reducing cAMP, and to Gβγ activating K⁺ channels to hyperpolarize the lactotroph, inhibiting Ca²⁺-dependent exocytosis ✓
- B D1 receptor; increases cAMP via Gαs, activating PKA to phosphorylate and inhibit prolactin gene transcription
- C D3 receptor; activates phospholipase C via Gαq, generating IP₃ that inhibits prolactin vesicle fusion
- D D4 receptor; directly opens Cl⁻ channels causing hyperpolarization
Correct answer: A. D2 receptor; couples to Gαi reducing cAMP, and to Gβγ activating K⁺ channels to hyperpolarize the lactotroph, inhibiting Ca²⁺-dependent exocytosis
Explanation
Lactotrophs express D2 receptors, which couple to Gαi (inhibiting adenylyl cyclase, reducing cAMP/PKA activity) and to Gβγ subunits that activate G-protein-coupled inwardly-rectifying K⁺ (GIRK) channels, hyperpolarizing the cell. Hyperpolarization reduces tonic L-type Ca²⁺ channel activity, preventing the Ca²⁺-dependent exocytosis of prolactin granules. This explains why D2 receptor agonists (bromocriptine, cabergoline) suppress prolactin in hyperprolactinemia, and why antipsychotics blocking D2 receptors cause hyperprolactinemia.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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