Inhibition of the cardiac response to sympathetic nerve stimulation by opioid peptides and its potentiation by morphine and methadone.
[D-Ala2,D-Leu5]enkephalin (1-10 microM) and [Met5]enkephalin-Arg-Phe (1-10 microM) produced concentration-dependent inhibition of the cardiac response to field stimulation of the adrenergic nerve terminals in preparations pretreated with peptidase inhibitors (captopril 10 microM, bestatin 10 microM, thiorphan 0.3 microM and L-leucyl-L-leucine 2 mM). The inhibitory response to the opioid agonists was evident in preparations superfused with solutions containing 1.8 mM calcium, but not in those containing 3.6 mM calcium. Moreover the inhibition was antagonized by naloxone 10 microM. [D-Ala2,Met5]enkephalinamide (1-3 microM) and beta-endorphin (1-3 microM) did not significantly affect the sympathetic response. The cardiac response to sympathetic stimulation was not inhibited but, on the contrary, was potentiated by morphine (3-10 microM) and methadone (3-10 microM). It is suggested that the depressant effect of the opioid peptides was due to stimulation of presynaptic inhibitory opiate receptors on adrenergic nerve terminals of the heart, and that the potentiation of the sympathetic response by morphine and methadone was probably attributable to an unspecific inhibitory effect on the neuronal uptake of noradrenaline.
D000818:Animals; D004357:Drug Synergism; D004558:Electric Stimulation; D004723:Endorphins / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D066298:In Vitro Techniques; D008297:Male; D008691:Methadone / Q000494:pharmacology*; D009020:Morphine / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000502:physiology*; D001615:beta-Endorphin
D004723:Endorphins; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D001615:beta-Endorphin; D016308:Enkephalin, Leucine-2-Alanine; C027511:enkephalin-Met, Arg(6)-Phe(7)-; D009020:Morphine; D008691:Methadone; D009638:Norepinephrine