Acute desensitization to angiotensin II: evidence for a requirement of agonist-induced diacylglycerol production during tonic contraction of rat aorta

European Journal of Pharmacology
N R Danthuluri, R C Deth

Abstract

A possible role for protein kinase C during the tonic phase of arterial contraction was examined in rat aorta by observing the effects of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), on angiotensin II (AII)-induced responses. The ability of AII and phenylephrine (PE) to induce diacylglycerol (DAG) production was monitored as agonist-stimulated 32P-labelling of phosphatidic acid (PA). AII (5 X 10(-7) M) causes only a transient contractile response, while PE (10(-5) M) causes a sustained tonic contraction. 32P-labelling studies showed that AII caused an initial increase of PA synthesis equal to PE, however, AII failed to sustain this increase at 5 and 10 min while PE was able to do so. This indicates a failure of AII to provide DAG to sustain protein kinase C activation. Activation of protein kinase C with TPA prior to and during AII exposure converted the normally transient contraction to a more sustained, tonic pattern. These results suggest that the capacity of neuroendocrine agonists to maintain tension is due to their ability to produce DAG continuously and thereby activate protein kinase C.

References

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Citations

Sep 23, 1987·European Journal of Pharmacology·N R DanthuluriR C Deth
Jan 1, 1988·Pharmacology & Therapeutics·S P Watson, P P Godfrey
May 23, 1995·Proceedings of the National Academy of Sciences of the United States of America·T MünzelD G Harrison
Apr 1, 1991·British Journal of Pharmacology·M S ResnickK G Morgan
Aug 30, 2012·The Journal of Physiology·Toshio Kitazawa, Kazuyo Kitazawa
Feb 15, 1988·Biochemical and Biophysical Research Communications·I WakabayashiK Nagai
Apr 10, 1991·European Journal of Pharmacology·M AuguetP Braquet
Oct 1, 1989·Medicinal Research Reviews·J C McGrathV G Wilson
Jan 1, 1990·The American Journal of Physiology·R M RapoportR F Highsmith
Nov 1, 1988·Molecular and Cellular Endocrinology·Y TakuwaH Rasmussen

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