Phosphoinositide metabolism in airway smooth muscle.
Contraction of airway smooth muscle (ASM) results from an increase in cytoplasmic free Ca2+ and appears to be independent of changes in membrane potential or the presence of extracellular Ca2+. Inositol 1,4,5-trisphosphate (Ins(1,4,5)P3), the product of receptor-mediated hydrolysis of a membrane phosphoinositide, phosphatidylinositol 4,5-bisphosphate, is capable of releasing Ca2+ from intracellular stores in this tissue and has been proposed as the intracellular second messenger responsible for agonist-induced changes in cytosolic Ca2+ and hence contraction. In this report, we discuss the evidence for this signaling system in ASM and present new data on mass changes in Ins(1,4,5)P3 in carbachol-stimulated bovine tracheal smooth muscle. The rapid, transient accumulation of this second messenger in ASM is thought to reflect regulation of the enzymes involved in the metabolism rather than the synthesis of this inositol polyphosphate. The potential mechanisms of this regulation are discussed in relation to the initiation and maintenance of contraction in ASM.
Chilvers
E R
ER
Department of Pharmacology and Therapeutics, University of Leicester, United Kingdom.
Nahorski
S R
SR
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism / Q000502:physiology; D007295:Inositol Phosphates / Q000378:metabolism; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000378:metabolism* / Q000502:physiology; D010716:Phosphatidylinositols / Q000378:metabolism*; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000378:metabolism; D015290:Second Messenger Systems
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium