title: Receptor subtype involved in alpha 1-adrenergic receptor-mediated Ca2+ signaling in cardiomyocytes.
abstract: OBJECTIVE
  The enhancement of intracellular Ca2+ signaling in response to alpha 1-adrenergic receptor (alpha 1-AR) stimulation is an essential signal transduction event in the regulation of cardiac functions, such as cardiac growth, cardiac contraction, and cardiac adaptation to various situations. The present study was intended to determine the role(s) of the alpha 1-AR subtype(s) in mediating this response.
  
  
  METHODS
  We evaluated the effects of subtype-specific agonists and antagonists of the alpha 1- AR on the intracellular Ca2+ signaling of neonatal rat ventricular myocytes using a confocal microscope.
  
  
  RESULTS
  After being cultured for 48 h, the myocytes exhibited spontaneous local Ca2+ release, sparks, and global Ca2+ transients. The activation of the alpha 1-AR with phenylephrine, a selective agonist of the alpha 1-AR, dose-dependently increased the frequency of Ca2+ transients with an EC50 value of 2.3 micromol/L. Blocking the alpha 1A-AR subtype with 5-methylurapidil (5-Mu) inhibited the stimulatory effect of phenylephrine with an IC(50) value of 6.7 nmol/L. In contrast, blockade of the alpha 1B-AR and alpha 1D-AR subtypes with chloroethylclonidine and BMY 7378, respectively, did not affect the phenylephrine effect. Similarly, the local Ca2+ spark numbers were also increased by the activation of the alpha 1-AR, and this effect could be abolished selectively by 5-Mu. More importantly, A61603, a novel selective alpha 1A-AR agonist, mimicked the effects of phenylephrine, but with more potency (EC(50) value =6.9 nmol/L) in the potentiation of Ca2+ transients, and blockade of the alpha 1A-AR by 5-Mu caused abolishment of its effects.
  
  
  CONCLUSIONS
  These results indicate that alpha 1-adrenergic stimulation of intracellular Ca2+ activity is mediated selectively by the alpha 1A-AR.
authors.affiliation: Department of Pharmacology, School of Chemical Biology and Pharmaceutical Sciences, Capital University of Medical Sciences, Beijing 100069, China. luodl@bjmu.edu.cn
authors.forename: Da-li
authors.initials: DL
authors.lastname: Luo
authors.forename: Jian
authors.initials: J
authors.lastname: Gao
authors.forename: Lin-lin
authors.initials: LL
authors.lastname: Fan
authors.forename: Yu
authors.initials: Y
authors.lastname: Tang
authors.forename: You-yi
authors.initials: YY
authors.lastname: Zhang
authors.forename: Qi-de
authors.initials: QD
authors.lastname: Han
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D007093:Imidazoles / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D013764:Tetrahydronaphthalenes / Q000378:metabolism
chemical_list: C094643:A 61603; D058646:Adrenergic alpha-1 Receptor Agonists; D058668:Adrenergic alpha-1 Receptor Antagonists; D007093:Imidazoles; D018340:Receptors, Adrenergic, alpha-1; D013764:Tetrahydronaphthalenes; D002118:Calcium