Studies of the interaction of 5-hydroxytryptamine and the perivascular innervation of the guinea-pig caecum.
1. The action and interaction of noradrenaline (NA), 5-hydroxytryptamine (5-HT) and the sympathetic innervation was studied in the isolated taenia of the guinea-pig caecum.2. Addition of 5-HT led to a contraction of the taenia while addition of NA or perivascular nerve stimulation resulted in relaxation. Responses to 5-HT or perivascular nerve stimulation were abolished by tetrodotoxin. Tetrodotoxin did not affect responses to applied NA. Hexamethonium and hyoscine converted the 5-HT response to a relaxation and augmented the relaxation which followed low frequency perivascular nerve stimulation. Hexamethonium and hyoscine did not affect the dose-response relationship for NA.3. Fatigue of mechanical responses of the taenia to perivascular nerve stimulation was accelerated when nerves were stimulated in the presence of 5-HT or alpha-methyl-p-tyrosine (alpha-MPT). These two agents were additive in this action.4. Reserpine, 6-hydroxydopamine and alpha-MPT all reduced the NA content of the taenia. However, only after 6-hydroxydopamine could adrenergic activity be related to NA content.5. Segments of taenia were incubated with either tritiated NA or 5-HT. An increased rate of release of radioactivity followed perivascular nerve stimulation after incubation with either substance. This release did not occur when tissue was taken from animals given reserpine or 6-hydroxydopamine.6. It is concluded that 5-HT activates neural elements exclusively while NA has a direct effect on smooth muscle. 5-HT can apparently be taken up by adrenergic axons, and appears to enter the releasable neurotransmitter pool. Since none of the actions characteristic of 5-HT are seen when it is released by adrenergic axons as a false neurotransmitter, the released amine probably fails to reach neuronal receptors for 5-HT.
D000200:Action Potentials; D000818:Animals; D002432:Cecum / Q000294:innervation*; D004298:Dopamine / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D006584:Hexamethonium Compounds / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D012110:Reserpine / Q000494:pharmacology; D012601:Scopolamine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists; D009435:Synaptic Transmission; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014443:Tyrosine / Q000494:pharmacology
D006584:Hexamethonium Compounds; D012702:Serotonin Antagonists; D012701:Serotonin; D014443:Tyrosine; D013779:Tetrodotoxin; D012110:Reserpine; D012601:Scopolamine; D004298:Dopamine; D009638:Norepinephrine