title: Signaling pathway and chronotropic action of parathyroid hormone in isolated perfused rat heart.
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 f ). However, it has been reported that PTH exerts its chronotropic effect via an interaction with adrenergic receptors or via L-type calcium channels. Thus, the objective of the study was to elucidate the exact mechanism of the chronotropic effect of PTH. We tested whether its chronotropic effects could be abolished by inhibitors of the following systems in isolated perfused rat hearts: alpha-adrenergic (prazosin); beta-adrenergic (propranolol); angiotensin II (CV11974); endothelin-1 (TAK044); calcium channel (verapamil); adenylyl cyclase (miconazole); phospholipase C (U73122) or I f (CsCl). In addition, we measured the cyclic adenosine monophosphate level of the heart after PTH administration. Whereas prazosin, propranolol, CV11974, TAK044, verapamil, and U73122 did not inhibit the chronotropic effect of PTH, CsCl or miconazole suppressed it significantly. PTH increased the cyclic adenosine monophosphate level of the atrium but not the left ventricle. These results indicate that the chronotropic actions of PTH are mediated via selective activation of adenylyl cyclase to increase the I f current.
authors.affiliation: Division of Cardiology, Department of Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Shimoyama
authors.forename: K
authors.initials: K
authors.lastname: Ogino
authors.forename: Y
authors.initials: Y
authors.lastname: Furuse
authors.forename: K
authors.initials: K
authors.lastname: Uchida
authors.forename: Y
authors.initials: Y
authors.lastname: Kinugasa
authors.forename: Y
authors.initials: Y
authors.lastname: Tomikura
authors.forename: O
authors.initials: O
authors.lastname: Igawa
authors.forename: I
authors.initials: I
authors.lastname: Hisatome
authors.forename: J P
authors.initials: JP
authors.lastname: Bilezikian
authors.forename: C
authors.initials: C
authors.lastname: Shigemasa
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology*; D013268:Stimulation, Chemical
chemical_list: D010281:Parathyroid Hormone; D000242:Cyclic AMP; D000262:Adenylyl Cyclases