Trophic influence of sympathetic neurons on the cardiac alpha-adrenergic response requires close nerve-muscle association.
In tissue culture, sympathetic neurons exert a trophic effect on myocardial cells to alter the alpha-adrenergic response from positive to negative chronotropism. We hypothesized that this neurotrophic effect might be a result of the release of a humoral substance into the bulk phase of the culture medium by the neurons. The negative chronotropic response to alpha stimulation persisted in nerve-muscle cultures pretreated with the muscarinic antagonist atropine, indicating that acetylcholine is not the trophic agent. Further, variations in the concentration of norepinephrine, epinephrine or dopamine in the nerve-muscle culture media do not account for the presence of a negative chronotropic response to alpha stimulation. Finally, muscle cells grown in the same petri dish with innervated muscle cells, to allow conditioning of the muscle cell environment by the neurons, do not acquire a negative chronotropic response to alpha stimulation. The results of this study clearly demonstrate that this trophic effect is not due to the release of a humoral substance into the bulk phase of the culture medium, but requires close nerve-muscle association. This suggests that the trophic effect may involve localized release and transsynaptic transfer of a chemical substance other than a neurotransmitter.
D000109:Acetylcholine / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002478:Cells, Cultured; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D006321:Heart / Q000294:innervation*; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014439:Tyramine / Q000494:pharmacology
D010656:Phenylephrine; D001285:Atropine; D000109:Acetylcholine; D009638:Norepinephrine; D014439:Tyramine