Drug‐induced changes in the release of [3H]‐noradrenaline from field stimulated rat iris

Abstract

Summary: Isolated rat irides were incubated with [3 H]‐noradrenaline [3 H‐NA] (10−7m), supervised with buffer and then stimulated by an electrical field. The effect of desipramine, clonidine, phentolamine, phenoxybenzamine, GD131, normetanephrine and 4‐tropolone‐acetamide on the stimulation‐induced overflow of [3 H]‐NA was tested by adding the drug to the super‐fusing buffer. The effect of pretreatment with phentolamine or phenoxybenzamine on the stimulation‐induced overflow of [3 H]‐NA was also studied. The effect of desipramine, clonidine, phentolamine, phenoxybenzamine and GD131 on uptake of [3 H]‐NA in isolated irides was determined. Desipramine moderately increased the stimulation‐induced overflow at concentrations which almost completely inhibited neuronal uptake. It was calculated that in the isolated rat iris 30–40% of the released [3 H]‐NA is inactivated by reuptake into the nerve terminal. This figure may represent the true reuptake percentage in this preparation. Desipramine‐induced inhibition of [3 H]‐NA release from the nerve terminal, possibly via a negative feed‐back mechanism, may also contribute to this low figure. Phentolamine and phenoxybenzamine, in concentrations or doses which did not inhibit neuronal uptake of [3 H]‐NA, consistently increased the stimulation‐induced overflow. This increase was further augmented when neuronal uptake was inhibited. The α‐adrenoceptor stimulating drug clonidine decreased the stimulation‐induced overflow. GD131, normetanephrine and 4‐tropolone‐acetamide did not greatly affect the stimulation‐induced overflow of [3 H‐NA]. It is concluded that the increased [3 H]‐NA overflow obtained after α‐adrenoceptor blockade is due to an increased [3 H]‐NA release from the nerve terminals.