title: Characterization of tachykinin mediated increases in [Ca2+]i in Chinese hamster ovary cells expressing human tachykinin NK3 receptors.
abstract: The nature of the senktide response of the human NK3 receptor expressed in Chinese hamster ovary cells was characterised using the Ca2+ sensitive dye Fura-2 and imaging methods. Application of the NK3 receptor agonist senktide caused an increase in [Ca2+]i in the cells. The profile for NK3 receptor agonists was that senktide was more potent than [beta-Ala8]neurokinin A-(4-10) which was more potent than [Sar9,Met(O2)11]substance P. SR 48968 was a poor antagonist of the senktide response in intact cells confirming the weak affinity of this agent for the NK3 receptor (IC50 of approximately 1 microM) shown in binding assays. The NK3 receptor mediated increase in intracellular Ca2+ was independent of [Ca2+]o, blocked by the microsomal Ca2+ ATPase inhibitor thapsigargin and the phospholipase C inhibitor U73122 but not by ryanodine. Thus the source of the Ca2+ was probably a ryanodine insensitive, inositol triphosphate sensitive intracellular store.
authors.affiliation: Parke Davis Neuroscience Research Centre, Addenbrookes Hospital Site, Cambridge, UK.
authors.forename: R D
authors.initials: RD
authors.lastname: Pinnock
authors.forename: N
authors.initials: N
authors.lastname: Suman-Chauhan
authors.forename: F Z
authors.initials: FZ
authors.lastname: Chung
authors.forename: L
authors.initials: L
authors.lastname: Webdale
authors.forename: Z
authors.initials: Z
authors.lastname: Madden
authors.forename: D R
authors.initials: DR
authors.lastname: Hill
authors.forename: G N
authors.initials: GN
authors.lastname: Woodruff
mesh_terms: D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D006224:Cricetinae; D003412:Cricetulus; D004963:Estrenes / Q000494:pharmacology; D016257:Fura-2 / Q000737:chemistry; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D008345:Manganese / Q000378:metabolism; D015288:Neurokinin A / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D012433:Ryanodine / Q000494:pharmacology; D015290:Second Messenger Systems; D013329:Structure-Activity Relationship; D013373:Substance P / Q000031:analogs & derivatives / Q000378:metabolism; D015320:Tachykinins / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
chemical_list: D001549:Benzamides; D004963:Estrenes; D007295:Inositol Phosphates; D010446:Peptide Fragments; D010880:Piperidines; D011760:Pyrrolidinones; D018042:Receptors, Neurokinin-3; D015320:Tachykinins; D013729:Terpenes; C054724:senktide; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D012433:Ryanodine; D013373:Substance P; D008345:Manganese; D019284:Thapsigargin; C073839:SR 48968; D015288:Neurokinin A; D010738:Type C Phospholipases; D000252:Calcium-Transporting ATPases; D002118:Calcium; D016257:Fura-2