Role of neuronal and extraneuronal uptake in responses of rabbit iris dilator muscle to levarterenol and phenylephrine.

The roles of neuronal and extraneuronal uptake mechanisms in the response of iris dilator muscles of rabbit to levarterenol (norepinephrine) and phenylephrine were investigated. Chemical denervation with 6-hydroxydopamine was used to eliminate neuronal uptake. Exposure to corticosterone prior to and during exposure to levarterenol or phenylephrine was used to assess the importance of extraneuronal uptake. Dose-response curves and ED50 values for levarterenol or phenylephrine in control and 6-hydroxydopamine-denervated tissues, both in the presence and absence of corticosterone, are shown. Curves illustrating the decay of tension on washout of levarterenol or phenylephrine from treated tissues were analyzed. 6-Hydroxydopamine denervation affected the response to levarterenol more than that to phenylephrine. Washout of both agonists was slower after 6-hydroxydopamine pretreatment, and washout of phenylephrine was more rapid when corticosterone was present. These data indicate that extraneuronal uptake in iris dilator muscles was more important in determining the response to phenylephrine than to levarterenol and that neuronal uptake was more important in determining tissue responsiveness to levarterenol than to phenylephrine.