title: β₃-Adrenergic regulation of L-type Ca²⁺ current and force of contraction in human ventricle.
abstract: β3-Adrenergic receptor (β3-AR) is expressed in human atrial and ventricular tissues. Recently, we have demonstrated that it was involved in the activation of L-type Ca(2+) current (I(Ca,L)) in human atrial myocytes and the force of contraction of human atrial trabeculae. In the present study, we examined the effect of β3-AR agonist CGP12177 which also is a β1-AR/β2-AR antagonist on I(Ca,L) in human ventricular myocytes (HVMs) and the force of contraction of human ventricular trabeculae. CGP12177 stimulated I(Ca,L) in HVMs with high potency but much lower efficacy than isoprenaline. The β3-AR antagonist L-748,337 inhibited the effect of CGP12177. CGP12177 and L748,337 competed selectively on β3-ARs because L748,337 had no effect on isoprenaline-induced stimulation of I(Ca,L), while CGP12177 completely blocked the effect of isoprenaline. The activation of β3-ARs by CGP12177 does not involve the activation of Gi proteins because CGP12177 had no effect on forskolin-induced stimulation of I(Ca,L). CGP12177 had no effect on the force of contraction of human ventricular trabeculae. L-NMMA, an inhibitor of NO synthase, and IBMX, a nonselective inhibitor of phosphodiesterases, did not potentiate the effect of CGP12177 either on contraction of human ventricular trabeculae or on I(Ca,L) in HVMs. We conclude that in human ventricles β3-AR activation has no inotropic effect, while it slightly increases I(Ca,L). In contrast to human atrium, the activation of β3-ARs in human ventricle is not accompanied by increased activity of phosphodiesterases.
authors: Institute of Cardiology, Lithuanian University of Health Sciences, 17 Sukilėlių Avenue, 50009, Kaunas, Lithuania.
authors: Rimantas
authors: R
authors: Treinys
authors: Danguolė
authors: D
authors: Zablockaitė
authors: Vida
authors: V
authors: Gendvilienė
authors: Jonas
authors: J
authors: Jurevičius
authors: V Arvydas
authors: VA
authors: Skeberdis
mesh_terms: D000293:Adolescent; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology; D058673:Adrenergic beta-3 Receptor Antagonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000627:Aminophenols / Q000494:pharmacology; D001696:Biomechanical Phenomena; D020746:Calcium Channels, L-Type / Q000502:physiology*; D020013:Calcium Signaling; D005260:Female; D006352:Heart Ventricles / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology; D022702:Receptors, Adrenergic, beta-3 / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D055815:Young Adult
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D058673:Adrenergic beta-3 Receptor Antagonists; D000627:Aminophenols; D020746:Calcium Channels, L-Type; C120576:L 748,337; D011412:Propanolamines; D022702:Receptors, Adrenergic, beta-3; D013449:Sulfonamides; D019001:Nitric Oxide Synthase; D010727:Phosphoric Diester Hydrolases; D007545:Isoproterenol; C033394:CGP 12177