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.
D000818:Animals; D002118:Calcium / Q000502:physiology; D002395:Catecholamines / Q000494:pharmacology*; D005576:Colforsin; D004224:Diterpenes / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000494:pharmacology*; D006321:Heart / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects
D002395:Catecholamines; D004224:Diterpenes; D011941:Receptors, Adrenergic; D005576:Colforsin; D009270:Naloxone; D004743:Enkephalin, Leucine; D007545:Isoproterenol; D002118:Calcium; D009638:Norepinephrine