Inositol 1,4,5-trisphosphate, inositide flux rates and pool sizes during smooth muscle relaxation.
Decreases in D-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] content and changes in inositol phospholipid contents occurred during the time of atropine-induced relaxation of swine tracheal smooth muscle contracted with 55 microM carbachol. Decrease in Ins(1,4,5)P3 occurred in a pool which makes up 40% of the total content of this inositol phosphate and which has access to Ins(1,4,5)P3 5-phosphatase and/or 3-kinase. A 50% decrease in this pool occurred at 16 s after addition of atropine and within 6-10 s after inhibition of phospholipase C (PLC). The maximal fall in Ins(1,4,5)P3 occurred at a time when force had only decreased 30% of the maximal response. A phosphatidylinositol 4-phosphate (PIP) pool linked to muscarinic receptor-activation increased 160% after addition of atropine, the maximal response occurring at a time when relaxation was 80% complete. The mechanisms for this increase were the maintained formation of PIP and phosphatidylinositol 4,5-bisphosphate (PIP2) even though PIP2 hydrolysis was inhibited and the apparent chemical equilibrium between PIP and PIP2.
Baron
C B
CB
Department of Physiology, University of Pennsylvania, Philadelphia 19104-6085.
Pompeo
J N
JN
Coburn
R F
RF
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D009126:Muscle Relaxation / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D010712:Phosphatidic Acids / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D013552:Swine; D014132:Trachea / Q000378:metabolism; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D001285:Atropine; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D010738:Type C Phospholipases