TY - JOUR
T1 - Sphingosine modulation of cAMP levels and beating rate in rat heart
AU - Benediktsdóttir, V. Edda
AU - Jónsdóttir, Anna M.
AU - Skúladóttir, Bergthóra H.
AU - Grynberg, Alain
AU - Skarphéoinsson, Jón Ó
AU - Helgason, Jóhannes
AU - Gudbjarnason, Sigmundur
PY - 2002
Y1 - 2002
N2 - Sphingolipids, especially as elements of the sphingomyelin signal transduction cycle, are thought to play a significant role as second messengers and modulators of events in heart muscle cells. A possible modulatory role of sphingosine in signal transduction in the β-adrenergic pathway in the heart was examined. Neonatal rat cardiomyocytes were incubated with sphingosine and/or other agents after which cAMP levels and contraction rates were measured. Heart rate in anaesthetized rats was also measured before and after sphingosine injection in the jugular vein. Sphingosine caused a decrease in basal cAMP levels and diminished isoproterenol-induced increase in cAMP levels. These changes were dose- and time-dependent and showed a significant negative effect on signal transmission in the β-adrenergic pathway in cardiomyocytes. Increase in cAMP intracellular levels by forskolin, which activates adenylcyclase, was not inhibited by sphingosine. A phosphodiesterase inhibitor was used in all experiments in which cAMP was measured excluding effects on cAMP breakdown. It was also demonstrated that sphingosine caused reduction in the beating rate of cultured cardiomyocytes and a dose-dependent reduction in heart rate of anaesthetized rats. The sphingosine-induced inhibition of bradycardic response of anaesthetized rats reached a maximum about 5-10 min after the onset of sphingosine administration and returned to normal within 60 min. Sphingosine may modulate the signal transmission of the β-adrenoceptor pathway upstream of adenylcyclase in rat cardiomyocytes. This may contribute to the sphingosine-induced decrease in heart rate of rats in vivo.
AB - Sphingolipids, especially as elements of the sphingomyelin signal transduction cycle, are thought to play a significant role as second messengers and modulators of events in heart muscle cells. A possible modulatory role of sphingosine in signal transduction in the β-adrenergic pathway in the heart was examined. Neonatal rat cardiomyocytes were incubated with sphingosine and/or other agents after which cAMP levels and contraction rates were measured. Heart rate in anaesthetized rats was also measured before and after sphingosine injection in the jugular vein. Sphingosine caused a decrease in basal cAMP levels and diminished isoproterenol-induced increase in cAMP levels. These changes were dose- and time-dependent and showed a significant negative effect on signal transmission in the β-adrenergic pathway in cardiomyocytes. Increase in cAMP intracellular levels by forskolin, which activates adenylcyclase, was not inhibited by sphingosine. A phosphodiesterase inhibitor was used in all experiments in which cAMP was measured excluding effects on cAMP breakdown. It was also demonstrated that sphingosine caused reduction in the beating rate of cultured cardiomyocytes and a dose-dependent reduction in heart rate of anaesthetized rats. The sphingosine-induced inhibition of bradycardic response of anaesthetized rats reached a maximum about 5-10 min after the onset of sphingosine administration and returned to normal within 60 min. Sphingosine may modulate the signal transmission of the β-adrenoceptor pathway upstream of adenylcyclase in rat cardiomyocytes. This may contribute to the sphingosine-induced decrease in heart rate of rats in vivo.
KW - Adrenergic receptors
KW - cAMP
KW - Cardiomyocytes
KW - Heart rate
KW - Sphingosine
UR - http://www.scopus.com/inward/record.url?scp=0036454710&partnerID=8YFLogxK
U2 - 10.1046/j.1472-8206.2002.00105.x
DO - 10.1046/j.1472-8206.2002.00105.x
M3 - Article
C2 - 12685508
AN - SCOPUS:0036454710
SN - 0767-3981
VL - 16
SP - 495
EP - 502
JO - Fundamental and Clinical Pharmacology
JF - Fundamental and Clinical Pharmacology
IS - 6
ER -