Lidocaine increases the number of beta-adrenoceptors in neonatal rat cardiocytes in culture.
Some physiological functions of the heart are modulated through cardiac beta-adrenoceptors. In acute myocardial infarction, ventricular arrhythmias occur frequently and class I antiarrhythmic drugs such as lidocaine are often administered continuously over long period. The aim of this study was to investigate the effects of long-term treatment with lidocaine on cardiac beta-adrenoceptors. Ventricular cardiocytes from 2-day-old Wistar rat were cultured in the presence or absence of lidocaine, and beta-adrenoceptors of the membrane fraction of the cells were measured with a binding assay using [125I]-iodocyanopindolol ([125I]CYP) as a radioligand. When the cells were cultured in the presence of lidocaine at clinical or toxic concentrations, the binding of [125I]CYP to the cells increased in a concentration (10(-5) mol/l-10(-3) mol/l)--and time (12-72 h)--dependent manner. The effect was due to an increase in maximum binding and was not due to a change in the dissociation constant for the ligand. The stimulation of adenylyl cyclase activity in the cell membrane by 1 mumol/l isoproterenol increased in lidocaine-treated cells. The increased number of receptors returned to the control level when the cells were cultured without lidocaine for a further 24 h. These results indicate that lidocaine up-regulates cardiac beta-adrenoceptors at both clinical or toxic doses during the period of treatment. Other antiarrhythmic drugs such as disopyramide (Ia), mexiletine (Ib) and flecainide (Ic) also increased the number of beta-receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Mizuki
T
T
Second Department of Medicine University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Kobayashi
H
H
Nakashima
Y
Y
Kuroiwa
A
A
Izumi
F
F
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D006321:Heart / Q000187:drug effects; D020120:Iodocyanopindolol; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D000889:Anti-Arrhythmia Agents; D011943:Receptors, Adrenergic, beta; D020120:Iodocyanopindolol; D008012:Lidocaine; D010869:Pindolol; D000262:Adenylyl Cyclases