The role of inositol 1,3,4,5-tetrakisphosphate in internal Ca2+ mobilization following histamine H1 receptor stimulation in DDT1 MF-2 cells.
Receptor-activated formation of inositol phosphates results in mobilization of intracellular stored Ca2+ in a variety of cells, including vas deferens derived DDT1 MF-2 cells. Stimulation of the histamine H1 receptor on these cells caused a pronounced formation of inositol 1,3,4,5-tetrakisphosphate (Ins(1,3,4,5)P4) with respect to that of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3). In this study, the role of inositol phosphates, in particular Ins(1,3,4,5)P4 on the internal Ca(2+)-releasing process was investigated in permeabilized and histamine-stimulated intact DDT1 MF-2 cells. In permeabilized cells. Ins(1,4,5)P3 induced a concentration-dependent release of intracellular stored Ca2+. Addition of Ins(1,3,4,5)P4 did not cause Ca2+ mobilization, but its presence enhanced the amount of Ca2+ released by Ins(1,4,5)P3, thereby increasing the total Ca(2+)-releasing capacity. The effect of both inositol phosphates was inhibited by heparin, known to block Ins(1,4,5)P3-sensitive receptors. Thus, the additional amount of Ca2+ released by Ins(1,3,4,5)P4 is mediated, either via Ins(1,4,5)P3-sensitive Ca2+ channels, or via different heparin-sensitive Ca2+ channels activated by both Ins(1,4,5)P3 and Ins(1,3,4,5)P4. Histamine H1 receptor stimulation in intact cells induced a Ca(2+)-dependent K+ current, representing Ca2+ release from internal stores if receptor-activated Ca2+ entry from the extracellular space was prevented under Ca(2+)-free conditions or in the presence of La3+. This transmembrane current was abolished in the presence of intracellularly applied heparin. Depletion of Ins(1,4,5)P3-sensitive Ca2+ stores by internal application of Ins(1,4,5)P3 reduced the histamine evoked K+ current to some extent if the contribution of external Ca2+ was excluded.(ABSTRACT TRUNCATED AT 250 WORDS)
Van der Zee
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L
Groningen Institute for Drug Studies (GIDS), Dept. of Clinical Pharmacology, University of Groningen, Netherlands.
Sipma
H
H
Nelemans
A
A
Den Hertog
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D012503:Saponins / Q000378:metabolism; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
D017442:Histamine Agonists; D007295:Inositol Phosphates; D012503:Saponins; C081655:inositol-1,3,4,5-tetrakisphosphate; D006632:Histamine; D002118:Calcium