ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract— In the human astrocytoma cell line U 373 MG, application of substance P (SP) leads to a transient increase in cytosolic calcium concentration and to a biphasic current response in voltage-clamped cells. Using these two functional assays we have characterized pharmacologically the SP response in U 373 MG cells. SP and [l-Pro9]SP displayed high potencies in both assays with EC50values of 2.5 ± 10−9M and 1 ± 10−9M on calcium responses and 110−9M and 510−9M on ion current responses, respectively. The high potency of SP and [l-Pro9]SP as well as the low potency of [Lys5,MeLeu9,N-Leu10]neurokinin A(4-10) and the inactivity of senktide demonstrate the NK1-type pharmacology of these responses. Furthermore, the NK1 antagonists (±)-CP 96,345, its chloro analogue, (±)-cis-3-(2-chlorobenzylamino)-2-benz-hydrylquinuclidine, and RP 67580 were potent antagonists of both SP responses. For the calcium mobilization induced by SP (1 (10−7M), the IC50 values for the three antagonists were 4 ± 10−10M, 4 ± 10−9M, and 9 ± 10−9M, respectively, whereas on the current response evoked by SP 10−8M), the IC50 values were 8 ± 10−9M, 2.4 ± 10−8M, and 1.2 10−7M, respectively. Despite differences in the absolute IC50 values obtained with both techniques, the relative potencies of the three antagonists correlate fairly well. The U 373 MG cell line provides a useful model system for studies of the pharmacology of the human NK1receptor and its transduction mechanisms at the level of second messengers and modulation of ion currents.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1471-4159.1993.tb09826.x
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