INOSITOL TRISPHOSPHATE AND ENERGY-FORCE COUPLING IN RABBIT AORTA

Five-minute exposures of aortic smooth muscle to 15 mu M norepinephrin e (NOR) under normoxia resulted in significant increases in inositol 1 ,4,5-trisphosphate [Ins(1,4,5)P-3] (152%), inositol 1,4-bisphosphate [ Ins(1,4)P-2] (171%) and inositol 4-phosphate [Ins(4)P] (203%) contents compared with values measured in unstimulated muscle but no changes i n inositol 1,3,4-trisphosphate [Ins(1,3,4)P-3], inositol 1,3,4,5-tetra kisphosphate [Ins(1,3,4,5)P-4] inositol 1/3-phosphate [Ins(1/3)P] or i nositol 1,3/3,4-bisphosphate [Ins(1,3/3,4)P-2] contents. Increases in Ins(1,4,5)P-3 content and the contents of its by-products persisted or increased for at least 20 min of NOR exposure during normoxia. After a rapid decrease in Po-2 at 5 min of NOR exposure, there were parallel decreases in Ins(1,4,5)P-3 and Ins(1,4)P-2 contents and in force. Ins (1,4,5)P-3 and Ins(1,4)P-2 contents were significantly decreased to 85 +/- 4.3% and 70 +/- 9.4% of control, respectively, at a time just aft er onset of relaxation. At near-maximal relaxation, Ins(1,4,5)P-3 and Ins(1,4)P-2 contents were decreased to 36.5 +/- 5.8% and 59.2, 16.8%, respectively, of control normoxia values (P<.05). After readmission of O-2 to the bubbling gas, Ins(1,4,5)P-3 and Ins(1,4)P-2 contents rapid ly increased. Comparing decreased Po-2-evoked [PCr] and [ATP] (phospho creatine and adenosine triphosphate) decrements (measured previously; Coburn et al., 1992) with our present data, threshold [PCr] and [ATP] for a decrease in Ins(1,4,5)P-3 content were shown to be 0.5 and 0.8 m M, respectively, and [PCr] and [ATP] at the time of 50% decrease in In s(1,4,5)P-3 content were 0.3 and 0.7 mM, respectively. We conclude tha t elevated Ins(1,4,5)P-3 contents and Ins(1,4,5)P-3 formation persist well into the force maintenance phase of NOR-evoked contractions, that decreases in [Ins(1,4,5)P-3] may drive relaxations evoked by decrease s in Po-2, that decrease in Ins(1,4,5)P-3 content was due to decreased formation and not increased degradation and that the inositol phospho lipid-inositol phosphate signal-transduction system be involved in ene rgy-force coupling of NOR-evoked aortic muscle contractions.