The anti-emetic action of the neurokinin(1) receptor antagonist CP-99,994 does not require the presence of the area postrema in the dog.
Microinjection and ligand binding studies have implicated NK(1) receptors in the area postrema (AP) in the emetic response to intragastric copper sulphate that is mediated by abdominal vagal afferents. Because these afferents terminate in the brainstem in the nucleus tractus solitarius in close proximity to the AP or in the AP itself, the results of such studies may be difficult to interpret. The present study has demonstrated in the dog that the emetic response to intragastric copper sulphate is unaffected by AP ablation, demonstrated functionally by absence of an emetic response to apomorphine (100 microg kg(-1) i.v.). In AP ablated animals the selective NK(1) receptor antagonist CP-99, 994 (1 mg kg(-1) i.v.) blocked the emetic response to copper sulphate as it did in intact animals. The results demonstrate that the AP is not involved in the blockade of the emetic response to intragastric copper sulphate by an NK(1) receptor antagonist and hence provides further support for other sites proposed such as the nucleus tractus solitarius and central pattern generator.
Andrews
P L
PL
Department of Physiology, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. pandrews@sghms.ac.uk
Kovacs
M
M
Watson
J W
JW
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D002628:Chemoreceptor Cells / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D019327:Copper Sulfate / Q000494:pharmacology; D003714:Denervation; D004285:Dogs; D004639:Emetics / Q000494:pharmacology; D020546:Fourth Ventricle / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology*; D018040:Receptors, Neurokinin-1 / Q000378:metabolism; D017552:Solitary Nucleus / Q000166:cytology / Q000502:physiology; D014630:Vagus Nerve / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D017833:Visceral Afferents / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D014839:Vomiting / Q000139:chemically induced / Q000503:physiopathology*
D000932:Antiemetics; D004639:Emetics; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018040:Receptors, Neurokinin-1; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D019327:Copper Sulfate; D001058:Apomorphine