Hypotensive action of synthetic fragments of parathyroid hormone.
Parathyroid hormone (PTH) and its N-terminal 1-34 fragment were shown to be hypotensive in dogs. In this study, synthetic bovine PTH fragments containing the N-terminal amino acids 1-34, 24-34, 24-28 and 25-27 [bPTH-(1-34), bPTH-(24-34), bPTH-(24-28) and bPTH-(24-27)] were synthesized and tested for hypotensive activity in dogs. bPTH-(1-34) is the most potent of these. The tripeptide is ineffective at doses as high as 2 mg/kg. bPTH-(24-34) and bPTH-(24-28) exhibited hypotensive activity but were less effective than bPTH-(1-34). A decrease in chain length decreased the hypotensive activity. The maximum response produced by bPTH-(1-34) was greater than that of either bPTH-(24-34) or bPTH-(24-28). The maximum responses, however, of bPTH-(24-34) and bPTH-(24-28) were similar. Another striking difference between bPTH-(1-34) and the other two effective fragments was the duration of action. Whereas the action of bPTH-(1-34) at ED50 lasted for up to 6 min the action of bPTH-(24-34) and bPTH-(24-28) lasted for less than 1 min. The hypotensive effect of these three bPTH fragments was not affected by propranolol, phentolamine, atropine, promethazine or cimetidine. In the perfused rat hindlimb, bPTH-(24-28) produced log dose-related sustained vasodilation.
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006728:Hormones / Q000138:chemical synthesis / Q000494:pharmacology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D000959:Antihypertensive Agents; D006728:Hormones; D010281:Parathyroid Hormone; D010455:Peptides