Inositol trisphosphate and energy-force coupling in rabbit aorta

H Matsumoto, CB Baron and RF Coburn

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

Five-minute exposures of aortic smooth muscle to 15 microM norepinephrine (NOR) under normoxia resulted in significant increases in inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] (152%), inositol 1,4- bisphosphate [Ins(1,4)P2] (171%) and inositol 4-phosphate [Ins(4)P] (203%) contents compared with values measured in unstimulated muscle but no changes in inositol 1,3,4-trisphosphate [Ins(1,3,4)P3], inositol 1,3,4,5-tetrakisphosphate [Ins(1,3,4,5)P4] inositol 1/3-phosphate [Ins(1/3)P] or inositol 1,3/3,4-bisphosphate [Ins(1,3/3,4)P2] contents. Increases in Ins (1,4,5)P3 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 Po2 at 5 min of NOR exposure, there were parallel decreases in Ins(1,4,5)P3 and Ins(1,4)P2 contents and in force. Ins(1,4,5)P3 and Ins(1,4)P2 contents were significantly decreased to 85 +/- 4.3% and 70 +/- 9.4% of control, respectively, at a time just after onset of relaxation. At near-maximal relaxation, Ins(1,4,5)P3 and Ins(1,4)P2 contents were decreased to 36.5 +/- 5.8% and 59.2 +/- 16.8%, respectively, of control normoxia values (P < .05). After readmission of O2 to the bubbling gas, Ins(1,4,5)P3 and Ins(1,4)P2 contents rapidly increased. Comparing decreased PO2-evoked [PCr] and [ATP] (phosphocreatine 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)P3 content were shown to be 0.5 and 0.8 mM, respectively, and [PCr] and [ATP] at the time of 50% decrease in Ins(1,4,5)P3 content were 0.3 and 0.7 mM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 270, Issue 2, pp. 708-712, 08/01/1994
Copyright © 1994 by American Society for Pharmacology and Experimental Therapeutics

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