Thiamylal and thiopental attenuate beta-adrenergic signaling pathway by suppressing adenylyl cyclase in rat ventricular myocytes.
The effects of intravenous anesthetics on myocytes have not been fully elucidated. To investigate the effects of various intravenous anesthetics such as fentanyl, morphine, ketamine, diazepam, midazolam, thiamylal, and thiopental on the beta-adrenergic signaling pathway, we measured isoproterenol-stimulated cyclic adenosine monophosphate (cAMP) production in freshly isolated rat ventricular myocytes. Fentanyl, morphine, ketamine, diazepam, and midazolam did not significantly affect isoproterenol-stimulated cAMP production. However, thiamylal and thiopental dose-dependently decreased cAMP production stimulated by isoproterenol or by forskolin, a direct adenylyl cyclase stimulator. In addition, we examined the role of protein kinase C (PKC) as a potential mediator of the thiamylal- or thiopental-induced effects on cAMP production using bisindolylmaleimide I, a non-specific PKC inhibitor. Bisindolylmaleimide I did not alter the inhibitory effects of thiamylal or thiopental. Thiamylal and thiopental significantly decreased isoproterenol-stimulated cAMP production by suppressing the adenylyl cyclase. We conclude that barbiturates such as thiamylal and thiopental decrease isoproterenol-stimulated cAMP production by suppressing the adenylyl cyclase through PKC-independent mechanisms.
Hidaka
Ikuhiro
I
Department of Anesthesiology and Critical Care, Division of Clinical Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. hikuhiro@hiroshima-u.ac.jp
Kurokawa
Hiromi
H
Yasuda
Toshimichi
T
Hamada
Hiroshi
H
Kawamoto
Masashi
M
Yuge
Osafumi
O
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D006352:Heart Ventricles / Q000187:drug effects*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013840:Thiamylal / Q000494:pharmacology*; D013874:Thiopental / Q000494:pharmacology*
D000067956:Adenylyl Cyclase Inhibitors; D006993:Hypnotics and Sedatives; D011943:Receptors, Adrenergic, beta; D013840:Thiamylal; D005576:Colforsin; D011493:Protein Kinase C; D013874:Thiopental; D007545:Isoproterenol