title: Purinergic P2X receptor activation induces emetic responses in ferrets and Suncus murinus (house musk shrews).
abstract: OBJECTIVE
  Despite the rapid progress made in understanding the significant role played by signalling via extracellular ATP in physiology and pathology, there has been no clear information generated on its involvement in the emetic response.
  
  
  METHODS
  In the present study, the emetogenic potential of extracellular ATP signalling in mammalian species was examined using ferrets and Suncus murinus (house musk shrews). A slowly degradable ATP analogue, alpha,beta-methyleneATP (alpha,beta-meATP), was used to activate the P2X receptors, and either the non-selective P2 receptor antagonist, pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), or the specific P2X(3) homomer and P2X(2/3) heteromer antagonist, A-317491, were tested against the agonist-induced response.
  
  
  RESULTS
  Intraperitoneal injection of alpha,beta-meATP produced significant emetic responses in ferrets (1 - 30 mg kg(-1)) and in Suncus murinus (5 - 50 mg kg(-1)). The responses occurred frequently within the first 10 min after administration, much less frequently from 11 to 60 min and no responses occurred later than 60 min. The emetic responses were completely inhibited by intraperitoneal pre-treatment with PPADS (100 mg kg(-1)) or A-317491 (100 mg kg(-1)). Abdominal surgical vagotomy did not reduce the emetic response in Suncus murinus significantly.
  
  
  CONCLUSIONS
  These results for the first time indicate that the activation of P2X receptors evokes emetic responses in mammalian species. The P2X(3) homomer and.or P2X(2/3) heteromer in the area postrema could be responsible for the emetic response. This finding contributes to the elucidation of the roles played by extracellular ATP signalling in various emetic symptoms.
authors: Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki, Japan. yukinori.nagakura@jp.astellas.com
authors: Y
authors: Y
authors: Nagakura
authors: S
authors: S
authors: Kakimoto
authors: N
authors: N
authors: Matsuoka
mesh_terms: D000255:Adenosine Triphosphate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005289:Ferrets; D007274:Injections, Intraperitoneal; D008297:Male; D023421:Models, Animal; D009325:Nausea / Q000503:physiopathology / Q000517:prevention & control; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology; D011083:Polycyclic Compounds / Q000008:administration & dosage / Q000494:pharmacology; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D012788:Shrews; D013045:Species Specificity; D013997:Time Factors; D014628:Vagotomy / Q000379:methods; D014839:Vomiting / Q000503:physiopathology* / Q000517:prevention & control
chemical_list: C470346:A-317491; D000970:Antineoplastic Agents; D010636:Phenols; D011083:Polycyclic Compounds; D058910:Purinergic P2 Receptor Agonists; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate
references: Pharmacol Rev. 2006 Mar;58(1):58-86
references: 16507883
references: Oncology. 1996 Jun;53 Suppl 1:8-17
references: 8692557
references: Regul Pept. 1996 Aug 27;65(1):45-53
references: 8876035
references: Neuropharmacology. 1996 Jan;35(1):91-7
references: 8684601
references: J Neurosci. 2003 Oct 1;23(26):8903-10
references: 14523092
references: Nature. 1995 Oct 5;377(6548):432-5
references: 7566120
references: Front Neuroendocrinol. 1994 Dec;15(4):301-20
references: 7895890
references: Auton Neurosci. 2006 Oct 30;129(1-2):3-16
references: 16934536
references: Pharmacol Toxicol. 1987 Sep;61(3):199-202
references: 3684952
references: Neuropharmacology. 1997 Sep;36(9):1229-42
references: 9364478
references: Arch Int Pharmacodyn Ther. 1984 Jan;267(1):131-40
references: 6721621
references: Annu Rev Pharmacol Toxicol. 2000;40:563-80
references: 10836147
references: Eur J Pharmacol. 2004 Nov 3;504(1-2):45-53
references: 15507220
references: Jpn J Pharmacol. 1993 Dec;63(4):415-21
references: 8121076
references: Brain Res. 1975 Jul 4;92(1):153-6
references: 1174942
references: Gastroenterology. 1952 Sep;22(1):1-12
references: 12980223
references: J Comp Neurol. 2000 Nov 27;427(4):485-507
references: 11056460
references: Biol Pharm Bull. 1997 May;20(5):486-9
references: 9178926
references: J Pharmacol Exp Ther. 2004 Jul;310(1):407-16
references: 15024037
references: Neuroscience. 2000;99(4):683-96
references: 10974431
references: Histochem Cell Biol. 2004 Aug;122(2):111-9
references: 15258768
references: J Physiol. 2000 Mar 1;523 Pt 2:403-11
references: 10699084
references: Br J Pharmacol. 2000 Jul;130(6):1247-54
references: 10903962
references: Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):17179-84
references: 12482951
references: Pain. 2002 Mar;96(1-2):99-105
references: 11932066
references: J Neurosci. 2004 May 19;24(20):4709-17
references: 15152030
references: Physiol Rev. 2002 Oct;82(4):1013-67
references: 12270951
references: Br J Pharmacol. 2006 Jul;148(6):845-52
references: 16770326
references: J Physiol. 2007 Jan 1;578(Pt 1):301-8
references: 17038431
references: Nature. 1995 Oct 5;377(6548):428-31
references: 7566119
references: Drugs Exp Clin Res. 1985;11(8):493-500
references: 3879753