Leucine-enkephalin increases norepinephrine-stimulated chronotropy and 45Ca++ uptake in guinea-pig atria

Norepinephrine (NE) (10(-5) M) increases the beating rate of isolated, spontaneously beating guinea-pig atria 78 +/- 3 beats per minute. Leucine-enkephalin (10(-7) M) increases the maximal chronotropic response to NE by 38%, i.e., by 30 beats per minute. In the presence of 10(-7) M leucine-enkephalin and 10(-7) M naloxone, the chronotropic response to NE is reduced to 38 +/- 3 beats per minute, a value observed in the presence of naloxone alone. Neither naloxone nor leucine enkephalin significantly altered the inotropic response to NE, or significantly altered the basal beating rate. Parallel effects were observed when 45Ca++ uptake by atrial tissue was examined. Incubation of atrial slices with 10(-5) M NE for 10 minutes minimally stimulated 45Ca++ uptake from 1.27 +/- 0.04 to 1.45 +/- 0.17 nmol/mg tissue. In the presence of 10(-7) M leucine-enkephalin, 45Ca++ uptake was increased to 1.95 +/- 0.14 nmol/mg tissue. 45Ca++ uptake was reduced to control values (1.19 +/- 0.09 nmol/mg tissue) in the presence of NE, leucine-enkephalin and naloxone (10(-7) M). The data are consistent with a leucine-enkephalin augmentation of NE-induced chronotropy in guinea-pig atria due to an enhancement of NE-dependent Ca++ accumulation. This effect of leucine-enkephalin is opposite that previously reported for rat atria, in which leucine-enkephalin inhibits both NE-induced positive chronotropy and Ca++ influx.