Studies of the interaction of 5‐hydroxytryptamine and the perivascular innervation of the guinea‐pig caecum

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Abstract
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 α-methyl-p-tyrosine (α-MPT). These two agents were additive in this action. 4 Reserpine, 6-hydroxydopamine and α-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.