Effects of heparin on inositol 1,4,5-trisphosphate and guanosine 5'-O-(3-thio triphosphate) induced calcium release in cultured smooth muscle cells from rabbit trachea.
The effects of heparin on intracellular calcium release in monolayers of permeabilised cultured rabbit smooth muscle cells were determined using 45Ca effluxes. Low molecular weight heparin inhibited inositol 1,4,5-trisphosphate (InsP3) induced Ca2+ release (IC50 = 0.8 microgram/ml), but not guanosine 5'-O-(3-thio triphosphate) (GTP gamma S) stimulated Ca2+ release. Only a small inhibition was noted with high molecular weight heparin and de-N-sulphated heparin, although chondroitin sulphate A potently inhibited the InsP3 response. These results indicate the competitive and specific nature of the heparin effect and give information about the structure of the InsP3 site.
Chopra
L C
LC
Department of Medicine, U.M.D.S., St Thomas' Hospital, London, UK.
Twort
C H
CH
Ward
J P
JP
Cameron
I R
IR
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D006493:Heparin / Q000494:pharmacology*; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008970:Molecular Weight; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D013329:Structure-Activity Relationship; D013403:Sugar Phosphates / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology*; D014132:Trachea
D007295:Inositol Phosphates; D013403:Sugar Phosphates; D013873:Thionucleotides; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D015544:Inositol 1,4,5-Trisphosphate; D006160:Guanosine Triphosphate; D006493:Heparin; D002118:Calcium