MolPharm xPharm- The Comprehensive Pharmacology Reference

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 Fethiere, J.
Right arrow Articles by De Lean, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fethiere, J.
Right arrow Articles by De Lean, A.

Pharmacological evidence for the heterogeneity of atrial natriuretic factor-R1 receptor subtype

J Fethiere and A De Lean

Department of Pharmacology, University of Montreal, Canada.

The atrial natriuretic factor-R1 (ANF-R1) receptor is known to mediate the biological effects of diverse natriuretic/diuretic/vasorelaxant peptides. In order to investigate the differential selectivity of this class of receptor, we have compared its pharmacological profile for various natriuretic peptides in rat, bovine, and human kidney. In contrast to bovine and rat, human kidney glomeruli do not express significant amounts of ANF-R2 receptor. In addition, the binding of 125I-labeled rat ANF-(99-126) to the ANF-R1 receptor in human and bovine kidney glomeruli is not blocked by rat ANF-(103-123) (pK less than 6), whereas in rat kidney glomeruli this peptide displays high affinity for the ANF-R1 receptor (pK = 8.5). This observation reveals a species heterogeneity between the rat and the human and bovine kidney receptors. In addition, we have observed striking differences in the pharmacological profiles of rat papillary, bovine papillary, and human kidney glomerular receptors, which contain only the 130-kDa ANF-R1 monomer. The bovine and human profiles were similar but diverged from that of the rat. In addition to the species heterogeneity of the ANF-R1 class, we could detect a significant intraspecies heterogeneity. Two distinct profiles could be disclosed, one having high affinity for both ANF and brain natriuretic peptide (BNP) and being identified in all three species studied and the other displaying lower affinity for BNP and being found in rat and human kidneys. We also demonstrate that rat and bovine papillary ANF-R1 receptors are coupled to guanylate cyclase and that ANF and BNP could activate the enzyme with potency similar to their potency in competing for 125I-labeled rat ANF-(99-126) binding. The results presented demonstrate that the ANF-R1 receptor class can be subclassified, based on distinct pharmacological profiles, and indicate a wide diversity within the ANF-R1 receptor family.

Volume 40, Issue 6, pp. 915-922, 12/01/1991
Copyright © 1991 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 © 1991 by the American Society for Pharmacology and Experimental Therapeutics