Regulation of phospholipase C activity by calcium ions and guanine nucleotide in the normoxic cat carotid body.
The carotid bodies (CB) are a paired chemoreceptor organ located at the bifurcation of the common carotid arteries. High O2 tension suppresses while low tension activates afferent carotid chemoreceptor activity and the chemoreflex ventilatory response in the cat. The intracellular mechanism of chemotransduction is till now unknown. Previously we have shown different activities of phospholipase C (PLC) in normoxic, hypoxic and hyperoxic cat carotid body. Now we have addressed the question whether calcium ions and G-protein could be regulators of the formation of lipid derived messenger molecules in the cat carotid body. To answer this question, the PLC acting against [3H] inositol-phosphatidylinositol (PtdIns) and [3H] inositol-phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2] in the cat CB were investigated using labelled phospholipids as a source of the substrate. CB homogenate was used as a source of the enzyme. The results indicate that PLC acting on PtdIns is Ca2+-dependent, in contrary to that acting on PtdIns(4,5)P2 which remains active in the presence of 10 mM EGTA. PtdIns(4,5)P2-PLC is stimulated by GTPgammaS. In the presence of Ca2+, GTPgammaS has a synergistic stimulatory effect. PLC acting on PtdIns is not activated by GTPgammaS. In the presence of calcium ions dopamine and a nonhydrozylable analogue of acetylcholine, carbachol, have a small stimulatory effect of about 30% on PLC acting on PtdIns(4,5)P2. GTPgammaS enhances this effect. These results allow us to suggest that there are two pathways of phosphoinositides degradation in the CB, one of them is regulated by calcium ions/PtdIns-PLC/, the other one by G-protein / PtdIns(4,5)P2-PLC/.
Strosznajder
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RP
Polish Academy of Science, Department of Neurophysiology Dr. Robert Strosznajder, Medical Research Center, Warsaw. roberts@cmdik.pan.pl
Pokorski
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M
D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002344:Carotid Body / Q000201:enzymology*; D002415:Cats; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D012016:Reference Values; D015398:Signal Transduction; D013379:Substrate Specificity; D010738:Type C Phospholipases / Q000378:metabolism*
D007295:Inositol Phosphates; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D010738:Type C Phospholipases; D002118:Calcium