Leucine-enkephalin Modulation of Catecholamine Positive Chronotropy in Rat Atria is Receptor-specific and Calcium-dependent

Leucine-enkephalin (LE) at 10(-8) M reduces the maximum chronotropic response of isolated spontaneously beating rat atria to exogenously added (-)-norepinephrine (NE) by approximately 27%, with no effect on the NE ED50 (1.5 X 10(-7) M) for positive chronotropy. This modulatory effect of LE is completely blocked by addition of 10(-7) M naloxone, and seems to be catecholamine-receptor specific, since the positive chronotropic response to forskolin is unaltered in the presence of LE. Isoproterenol (ISO)-induced positive chronotropy is also attenuated by LE. This effect is markedly dependent on the extracellular calcium concentration: LE actually causes a greater than two-fold enhancement of the positive chronotropic effect of ISO at low (0.5 mM) extracellular calcium concentration. A possible role for enkephalins to modulate catecholamine action on the heart via an alteration of catecholamine-induced inward calcium flux is discussed.