Dopamine D₂, but not D_4, receptor agonists are emetogenic in ferrets

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• 作者：Osinski ; Mark A. ; Uchic ; Marie E. ; Seifert ; Terese ; Shaughnessy ; Thomas K. ; Miller ; Loan N. ; et. al.
• 关键词：Calcium flux ; Dopamine receptors ; Dopamine agonists ; Ferrets ; Nausea ; Vomiting
• 刊名：Pharmacology, Biochemistry and Behavior
• 出版年：2005
• 出版时间：May, 2005
• 年：2005
• 卷：81
• 期：1
• 页码：211-219
• 全文大小：239 K

文摘

Agents that activate the dopamine D₂-like family of receptors elicit emesis in humans and other species with a vomiting/emetic reflex; however, the lack of dopamine receptor subtype selective agonists has hampered an understanding of which dopamine D₂-like receptor subtype(s) contributes to the emetic response. In this study, stable cell lines expressing the ferret dopamine D_2-long (D_2L) and D₄ receptors were used to characterize known dopamine agonists via radioligand binding and calcium ion flux assays, while emetic activity of these dopamine receptor agonists was determined in male ferrets. Latencies to first emetic event, average number of emetic episodes, and stereotypical behaviors which may be indicative of nausea were also determined. Agonists at dopamine D₁-like and D₄ receptors had no emetic effect in ferrets. Conversely, stimulation of dopamine D₂ and/or D₃ receptors resulted in a robust emetic response characterized by a relatively short latency (< 15 min) and multiple emetic events. Competitive antagonists of dopamine D₂-like receptors (domperidone, haloperidol) dose-dependently blocked the emetic response to PNU95666E, a dopamine D₂ receptor selective agonist. Thus, dopamine D₂ and/or D₃ receptor agonists elicit emesis, while dopamine D₁/D₅ or D₄ receptor-selective agonists are devoid of emetic properties.