Responses of rabbit aorta to tyramine in relation to the surface of drug entry.

The contraction elicited by submaximally effective concentrations of tyramine in the rabbit aortic strip occurs after a shorter latency and increases at a higher initial velocity to a greater steady-state level when drug entry is limited to the adventitial than when it is limited to the intimal surface. The reverse was true for noradrenaline. Both amines elicited equal maximum responses with independence of the surface of entry into the vascular wall. Differences between steady-state contractions disappear when the intramural disposition pathways of tyramine are blocked pharmacologically by a combination of pargyline and semicarbazide. Incubation with cocaine and pretreatment with reserpine resulted in a reversal of the surface of entry related differences between steady-state contractions to tyramine related to differences of the surface of entry. This reflected the unmasking of the direct component of the action of tyramine. Thus, the technique of limited drug entry into the vascular wall together with blockade of disposition pathways allows us to characterize the pre- and postsynaptic components of the action of tyramine.