Drug-induced changes in the release of ( 3 H)-noradrenaline from field stimulated rat iris

1. Isolated rat irides were incubated with [(3)H]-noradrenaline [(3)H-NA] (10(-7)M), superfused 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 superfusing buffer. The effect of pretreatment with phentolamine or phenoxybenzamine on the stimulation-induced overflow of [(3)H]-NA was also studied.2. The effect of desipramine, clonidine, phentolamine, phenoxybenzamine and GD131 on uptake of [(3)H]-NA in isolated irides was determined.3. 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.4. 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.5. The alpha-adrenoceptor stimulating drug clonidine decreased the stimulation-induced overflow.6. GD131, normetanephrine and 4-tropolone-acetamide did not greatly affect the stimulation-induced overflow of [(3)H-NA].7. It is concluded that the increased [(3)H]-NA overflow obtained after alpha-adrenoceptor blockade is due to an increased [(3)H]-NA release from the nerve terminals.