ryanodine and senktide

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.

Topics: Animals; Benzamides; Calcium; Calcium-Transporting ATPases; CHO Cells; Cricetinae; Cricetulus; Estrenes; Fura-2; Humans; Inositol Phosphates; Manganese; Neurokinin A; Peptide Fragments; Piperidines; Pyrrolidinones; Receptors, Neurokinin-3; Ryanodine; Second Messenger Systems; Structure-Activity Relationship; Substance P; Tachykinins; Terpenes; Thapsigargin; Type C Phospholipases