JPET Introducing ALZET?ew Model 2006 Pump

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 Google Scholar
Google Scholar
Right arrow Articles by Varma, D. R.
Right arrow Articles by Chemtob, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Varma, D. R.
Right arrow Articles by Chemtob, S.

Endothelium- and beta-2 adrenoceptor-independent relaxation of rat aorta by tyramine and certain other phenylethylamines

DR Varma and S Chemtob

Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.

At concentrations higher than that required to produce maximal vasoconstriction, tyramine caused concentration-dependent relaxation of rat aortic strips contracted maximally by tyramine, norepinephrine, phenylephrine, 5-hydroxytryptamine, prostaglandin F2 alpha, endothelin, angiotensin II and potassium; isoproterenol did not relax potassium- contracted strips. The vasorelaxant effect of tyramine was not antagonized by propranolol, pindolol or nadolol, all of which markedly antagonized the effects of isoproterenol. The vasorelaxant activity of tyramine was endothelium-independent and not inhibited by hemoglobin, methylene blue or L-NG-nitro arginine; it did not exhibit tachyphylaxis and was neither inhibited by cocaine, guanethidine, reserpine and chemical sympathectomy nor by alpha adrenoceptor, dopamine receptor, 5- hydroxytryptamine receptor, histamine receptor and adenosine receptor antagonists. Inhibition of cyclooxygenase, lipoxygenase and monamine oxidase activities did not decrease the vasorelaxant activity of tyramine. The vasorelaxant effect of tyramine was not decreased by altering external calcium from 0.25 to 4 mM nor was it potentiated by nifedipine. Phenylethylamine was the minimum structural requirement for this propranolol-resistant vasorelaxant activity; beta-carbon and 3- ring hydroxylation abolished this activity, but N-methylation partly overcame the effect of beta-hydroxylation. The vasopressor effect of tyramine in anesthetized rat was reversed to vasodepressor effect by phenoxybenzamine plus propranolol. The propranolol-resistant vasorelaxant effect of tyramine was also confirmed on isolated human placenta arteries. At vasorelaxant concentrations, tyramine did not increase cyclic GMP and cyclic AMP but inhibited inositol-1,4,5- triphosphate. It is suggested that at high concentrations tyramine and related phenylethylamines cause endothelium- and beta-2 adrenoceptor independent vasorelaxation either via specific tyramine receptors or nonselectively.

Volume 265, Issue 3, pp. 1096-1104, 06/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics






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

Copyright © 1993 by the American Society for Pharmacology and Experimental Therapeutics.