Inositol lipid breakdown as a step in α-adrenergic stimulus-response coupling

1985 ◽  
Vol 68 (s10) ◽  
pp. 43s-46s ◽  
Author(s):  
Robert H. Michell
Keyword(s):  
Protein Kinase C ◽  
Cell Function ◽  
Receptor Activation ◽  
Stimulus Response ◽  
Kinase C ◽  
Inositol 1,4,5 Trisphosphate ◽  
Messenger Molecules ◽  
Hydrolysis Of ◽  
Major Mediator ◽  
Stimulation Of

1. A widespread, and maybe universal, response to stimulation of α-adrenoceptors is inositol lipid hydrolysis: the receptor-coupled event is probably hydrolysis of phosphatidylinositol 4,5-bisphosphate. This reaction generates two second messenger molecules. 2. Inositol 1,4,5-trisphosphate may be responsible for the intracellular mobilization of Ca2+ that has long been recognized as a major mediator of the effects of α-receptor activation. In addition, the released 1,2-diacylglycerol probably contributes to control of cell function through activation of protein kinase C.

scholarly journals Stimulation of the hydrolysis of phosphatidylinositol 4,5-bisphosphate and phosphatidylcholine by endothelin, a complete mitogen for Rat-1 fibroblasts

1990 ◽  
Vol 272 (3) ◽  
pp. 761-766 ◽  
Author(s):  
E E MacNulty ◽  
R Plevin ◽  
M J O Wakelam
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Endothelin 1 ◽  
Kinase C ◽  
Choline Phosphate ◽  
Rapid Generation ◽  
Endothelin 3 ◽  
Hydrolysis Of ◽  
Phosphatidylcholine Synthesis ◽  
Stimulation Of

The mitogenic activity of endothelin and its ability to stimulate PtdIns(4,5)P2 and phosphatidylcholine turnover in Rat-1 fibroblasts was studied. Stimulated incorporation of [3H]thymidine occurred in the absence of any other added growth factors. The endothelins stimulated rapid generation of both Ins(1,4,5)P3 and choline. Endothelin-1 and endothelin-2 were equipotent in stimulating both responses, but endothelin-3 was less potent. Endothelin-1-stimulated Ins(1,4,5)P3 generation reached a maximum at 5 s and then declined; however, the response was long-lived, with a 4.5-fold elevation over basal still observed after 15 min. Endothelin-stimulated choline generation was observed with no increase in choline phosphate; indeed, the apparent level of this metabolite fell after 30 min of stimulation, presumably due to the observed stimulation of phosphatidylcholine synthesis. The endothelin-stimulated increase in choline generation was abolished in cells where protein kinase C was down-regulated. However, endothelin-stimulated choline generation was greater than that observed in response to a protein kinase C-activating phorbol ester, raising the possibility that the peptide activates phospholipase D by both protein kinase C-dependent and -independent mechanisms.

The stimulation of inositol lipid metabolism that accompanies calcium mobilization in stimulated cells: defined characteristics and unanswered questions

1981 ◽  
Vol 296 (1080) ◽  
pp. 123-138 ◽  
Keyword(s):  
Calcium Concentration ◽  
Receptor Activation ◽  
Receptor Stimulation ◽  
Stimulus Response ◽  
Inositol Lipids ◽  
Inositol Phospholipid ◽  
Inositol Phospholipid Breakdown ◽  
Phosphatidylinositol 4 ◽  
Hydrolysis Of ◽  
Stimulation Of

It now appears to be generally agreed that the ‘phosphatidylinositol response’, discovered in 1953 by Hokin & Hokin, occurs universally when cells are stimulated by ligands that cause an elevation of the ionized calcium concentration of the cytosol. The initiating reaction is almost certainly hydrolysis of an inositol lipid by a phosphodiesterase. Phosphatidylinositol, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate all break down rapidly under such circumstances. However, we do not yet know which of these individual reactions is most closely coupled to receptor stimulation, nor do we know where in the cell it occurs. With many stimuli, inositol phospholipid breakdown is closely coupled to occupation of receptors and appears not to be a response to changes in cytosol [Ca 2+ ] : this provoked the suggestion that it may be a reaction essential to the coupling between activation of receptors and the mobilization of Ca 2+ within the cell. In a few situations, however, it appears probable that inositol lipid breakdown can occur as a result of the rise in cytosol [Ca 2+ ] that follows receptor activation: such observations gave rise to the alternative opinion that inositol lipid breakdown cannot be related to stimulus-response coupling at calcium-mobilizing receptors. It now seems likely that these two views are too rigidly polarized and that some cells probably display both receptor-linked and Ca 2+ -controlled breakdown of inositol lipids. Both may sometimes occur simultaneously or sequentially in the same cell.

Role of protein kinase C in α1-adrenergic regulation of aNa i in guinea pig ventricular myocytes

2000 ◽  
Vol 279 (4) ◽  
pp. H1661-H1668 ◽  
Author(s):  
Su-Hyun Jo ◽  
Chung-Hyun Cho ◽  
Soo Wan Chae ◽  
Chin O. Lee
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Guinea Pig ◽  
Ventricular Myocytes ◽  
Receptor Activation ◽  
Adrenergic Regulation ◽  
Kinase C ◽  
Gf 109203X ◽  
Stimulation Of

We investigated the role of protein kinase C (PKC) in α1-adrenergic regulation of intracellular Na+activity (aNa i) in single guinea pig ventricular myocytes. aNa i and membrane potentials were measured with the Na+-sensitive indicator sodium-binding benzofuran isophthalate and conventional microelectrodes, respectively, at room temperature (24–26°C) while myocytes were stimulated at a rate of 0.25–0.3 Hz. The PKC activator 4β-phorbol 12-myristate 13-acetate (PMA) decreased aNa i in a concentration-dependent manner. PMA (100 nM) produced a maximal decrease in aNa i of 1.5 mM from 6.5 ± 0.4 to 5.0 ± 0.4 mM (means ± SE, n = 12, P< 0.01). The PMA concentration required for a half-maximal decrease in aNa i was 0.46 ± 0.13 nM ( n = 3, P < 0.01). An inactive phorbol, 4α-phorbol 12-myristate 13-acetate, did not decrease aNa i. The decrease caused by PMA could be blocked by the PKC inhibitors staurosporine and bisindolylmaleimide I (GF-109203X). Stimulation of the α1-adrenoceptor with 50 μM phenylephrine decreased aNa i from 6.1 ± 0.3 to 4.6 ± 0.3 mM ( n = 11, P< 0.01). The decrease in aNa i produced by phenylephrine was blocked by pretreatment with staurosporine, GF-109203X, or PMA. The decrease in aNa i produced by PMA was not prevented by pretreatment with tetrodotoxin but was blocked by pretreatment with strophanthidin or high extracellular K+ concentration. The results suggest that α1-adrenergic receptor activation results in a decrease in aNa i via PKC-induced stimulation of the Na+-K+ pump in cardiac myocytes.

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