Not only dopamine D2 receptors involved in Peony-Glycyrrhiza Decoction, an herbal preparation against antipsychotic-associated hyperprolactinemia.
Clinical studies have demonstrated the effectiveness of an herbal preparation called Peony-Glycyrrhiza Decoction (PGD) in alleviating antipsychotic-induced hyperprolactinemia (hyperPRL). In the present study, we further examined the pharmacological action of PGD on prolactin (PRL) secretion using in vitro and in vivo models, with specific attention to the role of dopaminergic mediators and other sex hormones. Treatment with PGD at 1-5mg/ml significantly suppressed PRL secretion and synthesis in MMQ cells, a model of hyperPRL derived from pituitary adenoma cells. The suppressive effects were completely abolished by pretreatment with 10μM haloperidol, a dopamine D(2) receptor antagonist. Consistent with a D(2)-action, PGD did not affect PRL in rat pituitary lactotropic tumor-derived GH3 cells that lack the D(2) receptor expression but significantly increased the expression of D(2) receptors and dopamine transporters (DAT) in PC12 cells. In a rat model of hyperPRL, produced by repeated injection of the dopamine blocker metoclopramide (MCP), chronic PGD (2.5-10g/kg daily) significantly reduced elevated serum PRL. The reduction in magnitude was similar to that elicited by bromocriptine (BMT), a dopamine D(2) receptor agonist currently used for treatment of hyperPRL. Neither PGD nor BMT altered serum estradiol, but PGD reversed decreased serum progesterone to control level, whereas BMT did not. These results indicate that the anti-hyperPRL effects of PGD are associated not only with D(2) receptor and DAT modulation, but also with a normalization of other sex hormone dysfunction. This experimental evidence supports clinical use of PGD as an effective treatment of antipsychotic-induced hyperPRL.
School of Chinese Medicine, LKS Faculty of Medicine, the University of Hong Kong, Hong Kong, China.
Di
D
Wang
Hei Kiu
HK
Wong
Li
L
Zhang
Grainne M
GM
McAlonan
Xiao-Min
XM
Wang
Stephen Cho Wing
SC
Sze
Yi-Bin
YB
Feng
Zhang-Jin
ZJ
Zhang
D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology; D002460:Cell Line; D004195:Disease Models, Animal; D004298:Dopamine / Q000096:biosynthesis; D065127:Dopamine D2 Receptor Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism; D005260:Female; D006035:Glycyrrhiza / Q000737:chemistry*; D006220:Haloperidol / Q000494:pharmacology; D041743:Herb-Drug Interactions; D006966:Hyperprolactinemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D008787:Metoclopramide / Q000009:adverse effects; D016716:PC12 Cells; D029596:Paeonia / Q000737:chemistry*; D008517:Phytotherapy / Q000379:methods*; D010936:Plant Extracts / Q000037:antagonists & inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D011374:Progesterone / Q000378:metabolism; D011388:Prolactin / Q000096:biosynthesis / Q000378:metabolism; D011817:Rabbits; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*
D065127:Dopamine D2 Receptor Antagonists; D050483:Dopamine Plasma Membrane Transport Proteins; D010936:Plant Extracts; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D011374:Progesterone; D004958:Estradiol; D011388:Prolactin; D006220:Haloperidol; D008787:Metoclopramide; D004298:Dopamine