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
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.