Negative feedback regulation of noradrenaline release by nerve stimulation in the perfused cat's spleen: differences in potency of phenoxybenzamine in blocking the pre‐ and post‐synaptic adrenergic receptors

1. The effects of low concentrations of phenoxybenzamine (8·8 × 10⁻¹⁰ to 2·9 × 10⁻⁷ M) on responses and on noradrenaline overflow elicited by nerve stimulation were studied in the perfused cat's spleen. 2. In the presence of 8·8 × 10⁻¹⁰ M or 2·9 × 10⁻⁹ M phenoxybenzamine there was a significant reduction in responses to nerve stimulation while the overflow of the transmitter did not increase at the two frequencies of stimulation employed: 5 and 30 Hz. 3. In the presence of 2·9 × 10⁻⁸ M or 2·9 × 10⁻⁷ M phenoxybenzamine the responses to nerve stimulation were practically abolished and a significant increase in transmitter overflow was obtained at both frequencies of stimulation. The drug was more effective in increasing transmitter overflow at 5 Hz when compared with 30 Hz. 4. The higher effectiveness of phenoxybenzamine in blocking the post‐synaptic α‐receptor when compared with the blockade of the presynaptic α‐receptor that regulates transmitter release is compatible with the view that these two receptors are not identical. 5. A second alternative for the difference in effectiveness of phenoxybenzamine is that both types of α receptors are identical, but the spare receptor capacity for the presynaptic adrenergic receptors is higher than that of the post‐synaptic receptors.