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Fragment-specific actions of parathyroid hormone in isolated perfused rat hearts.
- Source :
- Calcified Tissue International; Aug2001, Vol. 69 Issue 2, p88-93, 6p
- Publication Year :
- 2001
-
Abstract
- Different regions within the parathyroid hormone (PTH) molecule are known to have different biological activities. In the heart, the physiological actions of the intact PTH molecule are known as positive chronotropy and coronary vasodilatation. However, it is unclear which region of the PTH exerts which physiological action in the heart. Therefore, to clarify this point, we examined the hemodynamic effect of intact PTH(1-84) and selected PTH analogs, namely, PTH(1-34), PTH(2-34), [Nle8, 18Tyr34]PTH(3-34), PTH(4-34), [Tyr34]PTH(7-34), and PTH(13-34) in isolated perfused rat hearts. Both PTH(1-84) and PTH(1-34) significantly increased heart rate and decreased coronary perfusion pressure. In contrast, neither PTH(2-34) nor [Nle8,18Tyr34]PTH(3-34) increased heart rate, but they did decrease coronary perfusion pressure. Peptides further truncated at the amino terminus, PTH(4-34), [Tyr34]PTH(7-34), and PTH(13-34), had no effect on hemodynamics. Furthermore, the protein kinase A inhibitor H89, but not the protein kinase C inhibitor H7, attenuated the hemodynamic effects of PTH(1-34) or PTH(2-34), while it prevented those of [Nle8,18Tyr34]PTH(3-34). These results clearly demonstrate that the first amino acid of PTH is essential for its chronotropic property whereas the first 3 amino acids of PTH are involved in its coronary vasodilatory action. Furthermore, protein kinase A, but not protein kinase C, appears to be involved in the chronotropic and coronary vasodilatory actions of PTH. [ABSTRACT FROM AUTHOR]
- Subjects :
- PROTEIN kinases
HEART beat
AMINO acids
VASODILATION
HEMODYNAMICS
BLOOD circulation
RODENTS
ANIMAL experimentation
COMPARATIVE studies
DOSE-effect relationship in pharmacology
HEART
RESEARCH methodology
MEDICAL cooperation
PARATHYROID hormone
PEPTIDES
PERFUSION
RATS
RESEARCH
TIME
EVALUATION research
Subjects
Details
- Language :
- English
- ISSN :
- 0171967X
- Volume :
- 69
- Issue :
- 2
- Database :
- Complementary Index
- Journal :
- Calcified Tissue International
- Publication Type :
- Academic Journal
- Accession number :
- 15246951
- Full Text :
- https://doi.org/10.1007/s002230010023