Formation of inositol polyphosphates in airway smooth muscle after muscarinic receptor stimulation.
The effect of muscarinic-receptor stimulation on [3H]inositol mono-, bis-, tris- and tetrakisphosphate (InsP1, InsP2, InsP3 and InsP4) accumulation was examined in bovine tracheal smooth muscle slices prelabeled with myo-[3H]inositol. Carbachol (0.1 mM) caused a rapid increase in [3H]InsP3 and [3H]InsP2 followed by delayed increases in [3H]InsP1 and [3H]InsP4 accumulation. Analysis of the [3H]InsP3 isomers by HPLC showed an immediate although transient increase in [3H]Ins(1,4,5)P3 with a progressive and sustained accumulation of [3H]Ins(1,3,4)P3. [3H]Ins(1,3,4)P3 was confirmed as the predominant (greater than 80%) [3H]InsP3 isomer present at 1 and 30 min using an enzymatic method which causes selective hydrolysis of Ins(1,3,4)P3. Lithium enhanced markedly the carbachol-stimulated accumulation of [3H]InsP1 and [3H]InsP2 with a lower potency than that observed in other tissues but had no significant influence on [3H]InsP3 or [3H]InsP4 values. These data support a role for Ins(1,4,5)P3 in initiating airway smooth muscle contraction and indicate the importance of the Ins(1,3,4,5)P4/Ins(1,3,4)P4 pathway in this tissue.
Chilvers
E R
ER
Department of Pharmacology, University of Leicester, England.
Batty
I H
IH
Barnes
P J
PJ
Nahorski
S R
SR
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002417:Cattle; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D008094:Lithium / Q000494:pharmacology; D009130:Muscle, Smooth / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects*; D014132:Trachea / Q000378:metabolism*
D007295:Inositol Phosphates; D011976:Receptors, Muscarinic; D002217:Carbachol; D008094:Lithium; D002118:Calcium