Abstract
The role of tachykinin NK-1 receptors in the area postrema (AP) in emesis was examined in ferrets. Strong c-fos-like immunoreactivity was observed in the AP and nucleus tractus solitalius (NTS) in cisplatin (10 mg/kg, i.p.)-treated animals, but not in control animals. The number of the central emetogen morphine-induced vomits and retches was remarkably reduced (95%) and that of the peripheral emetogen copper sulphate-induced vomits was significantly (54%) reduced by AP lesion. Pretreatment with the tachykinin NK-1 receptor antagonists HSP-117 (1.0 microg) and CP-99,994 (7.5 microg) into the AP decreased the numbers of vomits and retches induced by morphine and copper sulphate. These results suggest that NK-1 receptors in the AP are involved in the mechanism of emesis induced by morphine and copper sulphate.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antiemetics / pharmacology
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Antineoplastic Agents / pharmacology
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Benzofurans / pharmacology
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Chemoreceptor Cells / cytology
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Chemoreceptor Cells / drug effects*
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Chemoreceptor Cells / metabolism*
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Cisplatin / pharmacology
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Copper Sulfate / pharmacology
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Drug Interactions / physiology
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Ferrets
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Fourth Ventricle / cytology
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Fourth Ventricle / drug effects*
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Fourth Ventricle / metabolism*
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Male
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Medulla Oblongata / cytology
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Medulla Oblongata / drug effects*
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Medulla Oblongata / metabolism*
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Morphine / pharmacology
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Narcotics / pharmacology
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Neurokinin-1 Receptor Antagonists
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Neurons / cytology
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Neurons / drug effects
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Neurons / metabolism
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Piperidines / pharmacology
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Proto-Oncogene Proteins c-fos / drug effects
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Proto-Oncogene Proteins c-fos / metabolism
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Radioligand Assay
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Receptors, Neurokinin-1 / drug effects*
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Receptors, Neurokinin-1 / metabolism*
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Solitary Nucleus / cytology
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Solitary Nucleus / drug effects
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Solitary Nucleus / metabolism
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Substance P / metabolism
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Substance P / pharmacology
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Tachykinins / antagonists & inhibitors
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Tachykinins / metabolism*
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Tritium
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Vomiting / drug therapy
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Vomiting / physiopathology*
Substances
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Antiemetics
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Antineoplastic Agents
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Benzofurans
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Narcotics
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Neurokinin-1 Receptor Antagonists
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Piperidines
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Proto-Oncogene Proteins c-fos
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Receptors, Neurokinin-1
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Tachykinins
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Tritium
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3-(2-methoxybenzylamino)-2-phenylpiperidine
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Substance P
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Morphine
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HSP 117
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Copper Sulfate
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Cisplatin