Stored calcium modulates inositol phosphate synthesis in cultured smooth muscle cells.
Cytosolic Ca2+ concentrations ([Ca2+]cyt) and [3H]inositol phosphates ([3H]InsP) were correlated while varying the Ca2+ content of the sarcoplasmic reticulum (SR) in cultured A7r5 cells at rest and during activation with [Arg8]-vasopressin (AVP). Thapsigargin (TG) raised and superfusion with 0 Ca2+ lowered [Ca2+]cyt, but both treatments decreased SR Ca2+ and AVP-evoked Ca2+ transients. Neither TG nor 0 Ca2+ affected basal [3H]InsP, but both treatments increased AVP-evoked synthesis of [3H]InsP. Exposure for several minutes to 40 mM K+ solution, BAY K 8644, or low-Na+ solution all elevated [Ca2+]cyt and, thereby, increased SR Ca2+, as manifested by augmented AVP-evoked Ca2+ transients. In all three cases, AVP-evoked, but not basal, [3H]InsP were reduced. The inhibitory effect of 40 mM K+ on AVP-evoked [3H]InsP synthesis was blocked when SR Ca2+ uptake was prevented by TG. Brief (30-s) exposures to 40 mM K+, which elevated [Ca2+]cyt but not SR Ca2+ loading, did not modify AVP-evoked [3H]InsP synthesis or Ca2+ transients. These results demonstrate an inverse relationship between SR Ca2+ content and evoked [3H]-InsP synthesis. Moreover, they suggest that SR Ca2+ may serve as a signal that modulates sarcolemmal [3H]InsP formation.
Berman
D M
DM
Department of Physiology, University of Maryland School of Medicine, Baltimore 21201.
Goldman
W F
WF
D001127:Arginine Vasopressin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D007295:Inositol Phosphates / Q000096:biosynthesis*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009994:Osmolar Concentration; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin; D014018:Tissue Distribution
D007295:Inositol Phosphates; D013729:Terpenes; D001127:Arginine Vasopressin; D019284:Thapsigargin; D002118:Calcium