JPET

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cherry, P. D.
Right arrow Articles by Gillis, C. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cherry, P. D.
Right arrow Articles by Gillis, C. N.

Antagonism of acetylcholine-mediated relaxation of rabbit pulmonary arteries by phorbol myristate acetate

PD Cherry and CN Gillis

Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut.

We studied the effect of 4-phorbol 12-myristate 13-acetate (PMA) on endothelium-dependent relaxation of rabbit isolated lobar pulmonary arteries contracted with phenylephrine. After full development of relaxation in response to 1.0 microM acetylcholine, addition of 10.0 nM PMA reversed relaxation rapidly and completely. This effect of PMA on acetylcholine-induced relaxation was unchanged when catalase was included in the medium. In separate groups of experiments, lobar pulmonary arteries were preincubated with 10.0 nM PMA for 20 min and then challenged with acetylcholine without washout of PMA. In these experiments PMA did not block completely the relaxation in response to addition of 1.0 microM acetylcholine. Log-concentration response curves for 0.01 to 31.6 microM acetylcholine vs. relaxation as percentage of phenylephrine-induced tone exhibited rightward shifts and depression of maxima after pretreatment with PMA. The EC50 for acetylcholine-induced relaxation was increased from 57 +/- 9.0 to 377 +/- 6.30 nM (values are mean +/- S.E.). Relaxation of lobar pulmonary arteries induced by 10.0 nM A23187 was much less sensitive to treatment with PMA than relaxation induced by acetylcholine. At least for the low concentration of PMA used here, these data are consistent with the following: 1) PMA blocks acetylcholine-induced relaxation by disrupting the link between acetylcholine receptor occupancy and the formation or release of the endothelium-derived relaxing factor, 2) PMA does not directly block the relaxant action of endothelium-derived relaxing factor on vascular smooth muscle and 3) the effect of PMA on acetylcholine-induced relaxation is not mediated by hydrogen peroxide or derived oxygen radicals.

Volume 247, Issue 2, pp. 542-546, 11/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 ChestHome page
S. J. Hutchison, R. E. Sievers, B.-Q. Zhu, Y.-P. Sun, D. J. Stewart, W. W. Parmley, and K. Chatterjee
Secondhand Tobacco Smoke Impairs Rabbit Pulmonary Artery Endothelium-Dependent Relaxation
Chest, December 1, 2001; 120(6): 2004 - 2012.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
Y. Ohara, H. S. Sayegh, J. J. Yamin, and D. G. Harrison
Regulation of Endothelial Constitutive Nitric Oxide Synthase by Protein Kinase C
Hypertension, March 1, 1995; 25(3): 415 - 420.
[Abstract] [Full Text]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1988 by the American Society for Pharmacology and Experimental Therapeutics.