Low Concentrations of the Stable Prostaglandin Endoperoxide U44069 Stimulate Shape Change in Quin2-loaded Platelets Without a Measurable Increase in [Ca2+]i
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Dose-response relationships for raised cytoplasmic free calcium concentration, [Ca2+]i, and shape change were measured simultaneously in quin2-loaded human platelets. With the calcium ionophore ionomycin the threshold [Ca2+]i for shape change was 300 nM with a maximal response at 800 nM. With 1 mM external Ca2+ the U44069 concentrations required to stimulate half-maximal shape change and an increase in [Ca2+]i were 2 and 41 nM, respectively. For PAF these values were 8.7 and 164 pg/ml, respectively. Low concentrations of U44069 and PAF evoked substantial shape change without any rise in [Ca2+]i. In the absence of external Ca2+, U44069 stimulated half-maximal shape change at 2 nM, and half-maximal elevation of [Ca2+]i at 69 nM: here, increased [Ca2+]i never reached the threshold [Ca2+]i for shape-change derived with ionomycin. These results suggest that some transduction mechanism other than elevated [Ca2+]i, as yet unidentified, can cause shape change.
Reddi B, Iannella S, OConnor S, Deane A, Willoughby S, Wilson D Intensive Care Med Exp. 2015; 3(1):37.
PMID: 26215804 PMC: 4512995. DOI: 10.1186/s40635-014-0037-7.
Minuz P, Fumagalli L, Gaino S, Tommasoli R, Degan M, Cavallini C Biochem J. 2006; 400(1):127-34.
PMID: 16859489 PMC: 1635449. DOI: 10.1042/BJ20061015.
Klages B, Brandt U, Simon M, Schultz G, Offermanns S J Cell Biol. 1999; 144(4):745-54.
PMID: 10037795 PMC: 2132941. DOI: 10.1083/jcb.144.4.745.
Ohkubo S, Nakahata N, Ohizumi Y Br J Pharmacol. 1996; 117(6):1095-104.
PMID: 8882602 PMC: 1909782. DOI: 10.1111/j.1476-5381.1996.tb16702.x.
Fluorescence and bioluminescence measurement of cytoplasmic free calcium.
Cobbold P, Rink T Biochem J. 1987; 248(2):313-28.
PMID: 3325037 PMC: 1148544. DOI: 10.1042/bj2480313.