Regulation of cytosolic calcium by angiotensins in vascular smooth muscle.
The carboxy terminal homologue of angiotensin II (Ang II), Ang-(3-8) or hexapeptide, was used as a model peptide to examine the types of receptor mechanisms involved in calcium mobilization in cultured vascular smooth muscle cells. Hexapeptide did not produce tachyphylaxis but did produce a sustained increase in intracellular calcium. Differences in the increase in intracellular calcium [( Ca2+]i) and the pattern of inositol phosphate production indicate that Ang-(3-8) and maximal concentrations of Ang II mobilize calcium through different mechanisms. The calcium-mobilizing mechanisms that predominate appear to depend on the concentration of angiotensin. Concentrations of Ang II greater than 10(-8) M produce sharp calcium transients in which the [Ca2+]i returns close to baseline within 1 minute after stimulation, but concentrations of Ang II equal to or less than 3 x 10(-9) M result in a plateau increase in calcium. Pretreatment with Bordetella pertussis toxin does not abolish either the calcium transient induced by Ang II or the plateau phase induced by Ang-(3-8), indicating that the GTP-transducing protein that couples the receptor to phospholipase C or, possibly, a receptor-operated calcium channel is not Bordetella pertussis toxin sensitive.
Dostal
D E
DE
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville 22908.
Murahashi
T
T
Peach
M J
MJ
D000809:Angiotensins / Q000502:physiology*; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology; D001884:Bordetella; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D011503:Transglutaminases; D010566:Virulence Factors, Bordetella
D000809:Angiotensins; D001427:Bacterial Toxins; D007295:Inositol Phosphates; D010566:Virulence Factors, Bordetella; C060969:dermonecrotic toxin, Bordetella; D004533:Egtazic Acid; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D002118:Calcium