Relaxation of splenic strips during wash out with amine-free solution after an exposure to noradrenaline

1. Strips were prepared from the spleens of normal or of reserpine-pretreated cats or rabbits. The strips were first exposed to (-)noradrenaline and then washed out with amine-free solution. 2. After inhibition of monoamine oxidase by pargyline "secondary sensitization" was prominent during the incubation with noradrenaline, and the early phase of quick relaxation was followed by a late phase of slow relaxation. The latter was cocaine-sensitive and has to be attributed to a slowly declining efflux of noradrenaline from adrenergic nerve endings. 3. Inhibition of catechol-O-methyl transferase by U-0521 or inhibition of extraneuronal uptake by hydrocortisone (cat) or corticosterone (rabbit) failed to alter relaxation. Apparently, an efflux of noradrenaline from extraneuronal stores plays little or no role in the relaxation of splenic strips. 4. During prolonged exposure to noradrenaline strips become desensitized to noradrenaline; on wash out of the amine, sensitivity is restored. As a consequence of this temporary desensitization the response to noradrenaline is not well maintained during prolonged exposure to this amine (when MAO is intact), and the relaxation curve is distorted (whenever a late phase of slow relaxation is prominent). 5. Indometacin enhances the sensitivity of rabbit (but not of cat) splenic strips to noradrenaline but fails to substantially alter relaxation curves. 6. When the distribution of noradrenaline is restricted to the extracellular space and when the concentration of the amine is varied over a wide range, essentially parallel relaxation curves are obtained on wash out, provided the initial contraction does not exceed 80% of maximum. For higher initial contractions relaxation is slowed during the first minute of wash out, probably because of the sigmoid shape of the dose-response curve.