Involvement of ß₂-Adrenergic Receptors in the Potentiation of the Chronotropic Action of Isoprenaline Evoked in Rocker-Cultured Neonatal Rat Heart Cells by Pyruvate and L(+)-Lactate

Abstract

Some time ago we reported (1) that cells from the ventricles of newborn rats, cultured as monolayers on the bottom of flasks that were continuously agitated on a rocking tray for insuring an adequate supply of oxygen (2) had a lower lactate content than did their counterparts in stationary (immobile) culture. The lowered lactate level was associated with subsensitivity to ß-adrenergic stimulation in terms of chronotropic responsiveness. Prior exposure of the rocked cells to L(+)-lactate (1–10 mM) or pyruvate (1 mM) for a minimum of 45–60 min led to a potentiation of the chronotropic response to the ß-adrenergic agonist isoprenaline by several orders of magnitude (3); causing the cells at 3 mM L(+)-lactate and 1 mM pyruvate to become even supersensitive to this catecholamine. The potentiation was abolished by low concentrations of propranolol, indicating involvement of ß-adrenergic receptors in this phenomenon. In the following we present data indicating that the receptors involved in the potentiation are of the ß₂ subtype and we present evidence suggesting that treatment with pyruvate and lactate makes these receptors, which otherwise appear to be inaccessible to isoprenaline, available for activation by this ß agonist.