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Common phosphatidylinositol 4,5-bisphosphate pools are involved in carbachol and serotonin activation of tracheal smooth muscle

CB Baron, J Pompeo, D Blackman and RF Coburn

Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia.

We examined the rate and extent of labeling of total cellular phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol (PI) in canine tracheal smooth muscle in response to maximum levels of two different contractile agonists, carbachol (5.5 microM) and serotonin (5-hydroxytryptamine, 5-HT) (47 microM) and when a second agonist was given during a maximal contraction evoked by the first agonist. Unstimulated tracheal smooth muscle strips were incubated with [3H]-myo-inositol (MI) to label tissue MI without much labeling of inositol phospholipids. With carbachol, there was a 20-fold increase in the [3H]-MI incorporation rate into inositol phospholipids, decreases in PI and PIP2 contents, and increases in phosphatidic acid and diacylglycerol contents. PI and PIP2 specific radioactivities reached plateaus, 0.90 +/- 0.03 and 0.80 +/- 0.04, respectively, compared with [3H]-MI specific radioactivity. 5-HT at 47 microM evoked smaller changes including force development, [3H]-MI incorporation rate and lipid mass changes. However, the plateau of PI and PIP2 labeling reached levels similar to that determined during carbachol-evoked force, 0.90 +/- 0.06 and 0.82 +/- 0.04, respectively. Carbachol (55 microM) addition after incubation with 5-HT did not significantly alter the plateau levels of the specific radioactivities of PI or PIP2, although force and lipid mass changes were significantly changed. We conclude that 5-HT and muscarinic receptor coupling mechanisms utilize the same pool of PIP2 as a substrate for phospholipase C activation and the same PI pool for conversion to PIP and PIP2.

Volume 266, Issue 1, pp. 8-15, 07/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1993 by the American Society for Pharmacology and Experimental Therapeutics.