Signaling pathway and chronotropic action of parathyroid hormone in isolated perfused rat heart

Citation
M. Shimoyama et al., Signaling pathway and chronotropic action of parathyroid hormone in isolated perfused rat heart, J CARDIO PH, 38(4), 2001, pp. 491-499
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Journal title
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
ISSN journal
0160-2446 → ACNP
Volume
38
Issue
4
Year of publication
2001
Pages
491 - 499
Database
ISI
SICI code
0160-2446(200110)38:4<491:SPACAO>2.0.ZU;2-Y
Abstract
Parathyroid hormone (PTH) activates both adenylyl cyclase and phospholipase C via the PTH-1 receptor. We previously reported that PTH increased heart rate and that this effect was mediated via the pacemaker current (I,). Howe ver, it has been reported that PTH exerts its chronotropic effect via an in teraction with adrenergic receptors or via L-type calcium channels. Thus, t he objective of the study was to elucidate the exact mechanism of the chron otropic effect of PTH. We tested whether its chronotropic effects could be abolished by inhibitors of the following systems in isolated perfused rat h earts: alpha -adrenergic (prazosin); beta -adrenergic (propranolol); angiot ensin II (CV11974); endothelin-1 (TAK044); calcium channel (verapamil); ade nylyl cyclase (miconazole); phospholipase C (U73122) or I-f (CsCl). In addi tion, we measured the cyclic adenosine monophosphate level of the heart aft er PTH administration. Whereas prazosin, propranolol, CV11974, TAK044, vera pamil, and U73122 did not inhibit the chronotropic effect of PTH, CsCl or m iconazole suppressed it significantly. PTH increased the cyclic adenosine m onophosphate level of the atrium but not the left ventricle. These results indicate that the chronotropic actions of PTH are mediated via selective ac tivation of adenylyl cyclase to increase the I-f current.