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)