Structure and vascular activity relationship of parathyroid hormone and some hypotensive peptides.
The synthetic fragment of bovine PTH [bPTH-(1-34)] had direct vasodilatory action in the coronary, renal, hepatic and some visceral vascular beds. The vascular action of bPTH-(1-34) was separable from its hypercalcemic action. We attempted to identify the amino acid sequence responsible for this vascular action. The methionines in positions 8 and 18 were not necessary for vascular relaxation since [Nle8, Nle18, Tyr34]-bPTH-(1-34) was active. However, when these methionine residues were oxidized, the vascular action of this peptide disappeared. This would suggest conformational changes of this oxidized peptide, resulting in loss of activity. Adjacent basic amino acids in positions 25, 26 and 27 may play an important role in the hypotensive action of peptides. Other hypotensive peptides such as neurotensin, xenopsin and VIP which also possess adjacent basic amino acids but are not known to be vasoactive were also hypotensive in our assays.
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001808:Blood Vessels / Q000187:drug effects*; D006801:Humans; D008715:Methionine / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D011487:Protein Conformation; D013329:Structure-Activity Relationship
D000959:Antihypertensive Agents; D010281:Parathyroid Hormone; D010455:Peptides; D008715:Methionine