SMOOTH-MUSCLE STRETCH-ACTIVATED PHOSPHOLIPASE-C ACTIVITY

Rabbit aortic muscles were stretched from a holding length of 0.6 maximum length (L(max)) to lengths as great as 1.0 L(max) and the new length maintained. When muscles were stretched to 1.0 L(max) inositol 1,4,5-trisphosphate [Ins(1,4,5)P-3] and inositol 1,4-bisphosphate [Ins(1,4)P-2] contents were increased at 375 ms (uncorrected for freezing time) poststretch to 209 +/- 27 and 139.8 +/- 12% (SE), respectively, of control values. Increases in Ins(1,4,5)P-3 and Ins(1,4)P-2 contents reached an apparent maximum at similar to 500 ms, i.e., to 243.7 +/- 15.8 and 180.9 +/- 16.2% of control, and were decreased to near control levels at 1,700 ms poststretch. The stretch threshold for phospholipase C (PLC) activation was 0.85 L(max). The latency to onset of PLC activation, correcting for the time for freezing, was 275 to 375 ms. Maximal PLC activity was 91 pmol.s(-1).100 nmol total lipid P-i(-1), which corresponded to 10% of total phosphatidylinositol bisphosphate being hydrolyzed per second. The mechanism of stretch-activated PLC activity involved influx of Ca2(+) via gadolinium-sensitive ion channels, but not via nifedipine-sensitive ion channels.