Summary
Effects of dynorphin-(1–13), Leu5-enkephalin,d-Ala2,d-Leu5-enkephalin (DADLE), and for comparison bremazocine, on plasma noradrenaline concentration and mean arterial pressure (MAP) were studied in pithed rabbits. In the first series of experiments, the sympathetic outflow was stimulated electrically via the pithing rod at 2 Hz twice for 3 min each (S1, S2). Drugs were administered before S2. Bremazocine 10 μg/kg+2μg/kg/h and 100 μg/kg+20 μg/kg/h, dynorphin 1 and 3 μg/kg/min, Leu5-enkephalin 100 μg/kg/min and DADLE 10 and 30 μg/kg/min all diminished the electrically-evoked increase in plasma noradrenaline and MAP. The effects were antagonized by naloxone. In the second series, an infusion of noradrenaline (2 μg/kg/min) was given twice for 3 min each (N1, N2). Drugs were administered before N2. Bremazocine 100 μg/kg+20 μg/kg/h slightly enhanced the pressor effect of exogenous noradrenaline, whereas dynorphin 3 μg/kg/min, Leu5-enkephalin 100 μg/kg/min and DADLE 30 μg/kg/min caused no significant change. In the third series, the sympathetic outflow was stimulated continuously at 2 Hz, and the interaction of dynorphin and DADLE was studied. Dynorphin 1 μg/kg/min and DADLE 10μg/kg/min initially decreased MAP to a similar extent. The effect of DADLE faded with time. When, during continuous infusion of DADLE 10 μg/kg/min, and after return of MAP to the pre-DADLE level, dynorphin 1 μg/kg/min or DADLE 10 μg/kg/min was infused additionally, the effect of dynorphin was unchanged, whereas that of DADLE was almost abolished. We conclude that the opioid peptides as well as bremazocine decrease action potential-evoked release of noradrenaline and, secondarily, blood pressure. They act at peripheral sites, presumably prejunctional opioid receptors at postganglionic sympathetic axons. Dynorphin on the one hand, and Leu5-enkephalin and DADLE on the other hand, appear to act at different receptors, dynorphin probably at a ϰ- and DADLE and Leu5-enkephalin at a δ-receptor.
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Szabo, B., Hedler, L., Ensinger, H. et al. Opioid peptides decrease noradrenaline release and blood pressure in the rabbit at peripheral receptors. Naunyn-Schmiedeberg's Arch. Pharmacol. 332, 50–56 (1986). https://doi.org/10.1007/BF00633196
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DOI: https://doi.org/10.1007/BF00633196