Characterization of tachykinin mediated increases in [Ca2+]i in Chinese hamster ovary cells expressing human tachykinin NK3 receptors.
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.
Pinnock
R D
RD
Parke Davis Neuroscience Research Centre, Addenbrookes Hospital Site, Cambridge, UK.
Suman-Chauhan
N
N
Chung
F Z
FZ
Webdale
L
L
Madden
Z
Z
Hill
D R
DR
Woodruff
G N
GN
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
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