Abstract

The intrinsic disposition (termination of action) of a concentration of phenylephrine which produced about half-maximal contractions of strips of rabbit aorta was assessed from the rates of relaxation after replacing the aqueous bathing medium with mineral oil to prevent loss of amine by diffusion out of the tissue. Rate of relaxation was reduced 90% by iproniazid and about 45% by cocaine or methyiphenidate. The effect of iproniazid appeared to be due entirely to inhibition of monoamine oxidase (MAO), although a related MAO inhibitor (pheniprazinc, JB-516) was shown to have additional actions affecting amine disposition. The effect of cocaine probably involved inhibition of uptake into adrenergic nerves, but its overlap with the effect of iproniazid appeared due to a generalized effect on transport across biologic membranes which limited access of amine to sites of inactivation in effector cells. Iproniazid plus cocaine completely prevented relaxation, indicating that MAO and the cocaine-sensitive mechanism(s) are the only processes capable of inactivating phenylephrine in this vascular smooth muscle preparation. In contrast to the relative effects on disposition, cocaine potentiated responses of aortic strips to phenylephrine much more than did iproniazid. Alternative explanations for this discrepancy are pointed out, and it is concluded that potentiation after inactivation of a pathway of agonist disposition may he a generally unreliable criterion of its importance in terminating the action of the agent in question.