COMMON PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE POOLS ARE INVOLVED IN CARBACHOL AND SEROTONIN ACTIVATION OF TRACHEAL SMOOTH-MUSCLE

Citation
Cb. Baron et al., COMMON PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE POOLS ARE INVOLVED IN CARBACHOL AND SEROTONIN ACTIVATION OF TRACHEAL SMOOTH-MUSCLE, The Journal of pharmacology and experimental therapeutics, 266(1), 1993, pp. 8-15
Citations number
39
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00223565
Volume
266
Issue
1
Year of publication
1993
Pages
8 - 15
Database
ISI
SICI code
0022-3565(1993)266:1<8:CP4PAI>2.0.ZU;2-9
Abstract
We examined the rate and extent of labeling of total cellular phosphat idylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol (PI) in canine tracheal smooth muscle in response to maximum levels of two dif ferent contractile agonists, carbachol (5.5 AM) and serotonin (5-hydro xytryptamine, 5-HT) (47 muM) and when a second agonist was given durin g a maximal contraction evoked by the first agonist. Unstimulated trac heal smooth muscle strips were incubated with [H-3]-myo-inositol (MI) to label tissue MI without much labeling of inositol phospholipids. Wi th carbachol, there was a 20-fold increase in the [H-3]-MI incorporati on rate into inositol phospholipids, decreases in PI and PIP2 contents , and increases in phosphatidic acid and diacylglycerol contents. PI a nd PIP2 specific radioactivities reached plateaus, 0.90 +/- 0.03 and 0 .80 +/- 0.04, respectively, compared with [H-3]-MI specific radioactiv ity. 5-HT at 47 muM evoked smaller changes including force development , [H-3]-MI incorporation rate and lipid mass changes. However, the pla teau of PI and PIP2 labeling reached levels similar to that determined during carbachol-evoked force, 0.90 +/- 0.06 and 0.82 +/- 0.04, respe ctively. Carbachol (55 muM) addition after incubation with 5-HT did no t significantly alter the plateau levels of the specific radioactiviti es of PI or PIP2, although force and lipid mass changes were significa ntly changed. We conclude that 5-HT and muscarinic receptor coupling m echanisms utilize the same pool of PIP2 as a substrate for phospholipa se C activation and the same PI pool for conversion to PIP and PIP2.