Arachidonic acid is functioning as a second messenger in activating the Ca2+ entry process on H1-histaminoceptor stimulation in DDT1 MF-2 cells

Abstract

This study was carried out to identify the cellular component activating the histamine-stimulated Ca2+ entry in vas-deferensderived DDT1 MF-2 cells. H1-histaminoceptor stimulation resulted in a rise in intracellular Ca2+ concentration, caused by Ca2+ release from inositol phosphate-sensitive Ca2+ stores and Ca2+ entry from the extracellular space, accompanied by a transient Ca2+-activated outward K+ current. The histamineevoked K+ current was still observed after preventing inositol phosphate-induced Ca2+ mobilization by intracellularly applied heparin. This current was activated by Ca2+ entry from the extracellular space, because it was abolished in the presence of the Ca2+-channel blocker La3+ or under Ca2+-free conditions. Hhistaminoceptor-activated Ca2+ entry was also observed in the presence ofintracellularly applied Ins(1,4,5)P3 and Ins(1,3,4,5)P4, depleting their respective Ca2+ stores and pre-activating the inositol phosphate-regulated Ca2+ entry. Thus the ability of histamine to activate Ca2+ entry independently of Ca2+ mobilization and the formation of inositol phosphates suggests that another component is involved to initiate the Ca2+-entry process.

Muscarinic Receptor Activation of Arachidonate-mediated Ca2+ Entry in HEK293 Cells Is Independent of Phospholipase C

“…The data further indicate that this is an effect of arachidonic acid itself and not of a product of the commonly recognized metabolic pathways for arachidonic acid. Regarding our data on the activation of Ca 2ϩ entry by exogenous application of arachidonic acid, such application has been reported to produce a variety of effects on [Ca 2ϩ ] i signals in a many different cells, including effects on Ca 2ϩ release from intracellular stores (28) as well as on Ca 2ϩ entry (29). However, most of these studies involved the use of very high concentrations of arachidonate (Ͼ50 M), raising the possibility of a variety of nonspecific effects.…”

Activation and priming of neutrophil nicotinamide adenine dinucleotide phosphate oxidase and phospholipase A2 are dissociated by inhibitors of the kinases p42ERK2and p38SAPK and by methyl arachidonyl fluorophosphonate, the dual inhibitor of cytosolic and calcium-independent phospholipase A2

“…18 Arachidonate may also facilitate the formation of the NADPH oxidase complex on the membrane by enabling the translocation of cytosolic proteins, 19 increasing the affinity of guanosine 5Ј-triphosphate (GTP) binding sites in the plasma membrane, 20 and enhancing the dissociation of the rac G protein from its regulatory molecule, GDI. 21 Additionally, arachidonate may act as a signal transduction molecule by activating protein kinase cascades, such as protein kinase C, 22,23 mitogen-activated protein kinase (MAPK), p42 ERK2 , 23,24 and stress-activated protein kinase, p38 SAPK , 23 or by modulating intracellular calcium levels 25,26 upstream from the NADPH oxidase. AA that is required for NADPH oxidase activity may derive from several lipid sources through the activity of PLA 2 .…”

Characteristics of the Ca2+‐dependent inhibition of cyclic AMP accumulation by histamine and thapsigargin in human U373 MG astrocytoma cells

“…The converse is certainly true, namely that increases in [Ca 2+ ] i do not necessarily lead to inhibition/activation of Ca 2+ -sensitive cyclases (Chiono et al, 1995;Fagan et al, 1998;Shuttleworth & Thompson, 1999). In the great majority of studies in which multiple pathways have been identi®ed, such as those cited above (Clementi et al, 1992;Montero et al, 1994;van der Zee et al, 1995;Kass et al, 1994;Kiang, 1997;Iwamuro et al, 1998;Broad & Taylor, 1999) or those described in Wayman et al (1996) or in Parekh & Penner (1997), measurements were made either of whole cell currents or of changes in [Ca 2+ ] i . It is the great advantage of the approach adopted here that the characteristics of Ca 2+ entry coupled to inhibition are inferred from the response of the eector.…”

“…There have been a number of studies on other preparations which have demonstrated that agonists at G protein-coupled receptors can stimulate Ca 2+ entry through two or more channels with diering sensitivity to lanthanides and divalent cations (Clementi et al, 1992;Montero et al, 1994;van der Zee et al, 1995;Kass et al, 1994;Kiang, 1997;Iwamuro et al, 1998;Broad & Taylor, 1999). There is also good evidence from the cloning of human analogues of the trp and trpl channels, which are involved in photoreception in Drosophila (Hardie & Minke, 1993;Niemeyer et al, 1996), for Ca 2+ permeable channels, which are not activated by thapsigargin, but which can be activated by receptors coupled to G q/11 (Okada et al, 1998;Boulay et al, 1997), including the histamine H 1 -receptor (Hofmann et al, 1999).…”

“…Which of these channels are expressed in U373 MG cells and, if so, whether the coupling between G q/11 and Ca 2+ entry is via a direct action of diacylglycerol (Hofmann et al, 1999), has not yet been established. There is also evidence that histamine can stimulate Ca 2+ entry in DDT 1 MF-2 cells via the intermediate formation of arachidonic acid (van der Zee et al, 1995), which can be derived from diacylglycerol, as in A7r5 cells (Broad & Taylor, 1999), but this seems a less likely pathway for mediating the inhibitory action of histamine in view of the evidence that in HEK 293 cells arachidonic acid-induced Ca 2+ entry is ineective in potentiating the activation of the type VIII cyclase, whereas capacitative Ca 2+ entry does so (Shuttleworth & Thompson, 1999).…”