Abstract

The mechanism has been examined by which phenoxybenzamine causes an excessive overflow of norepinephrine (NE) liberated by sympathetic stimulation of the isolated cat colon. The results show that phenoxybenzamine prevents the reincorporation of nerve-liberated NE by preventing the transmitter from combining with the adrenergic receptor rather than by a direct action on the nerve ending. This action makes phenoxybenzamine an invaluable tool for studies of sympathetic nerve endings, since the amount of NE escaping into the blood stream may represent the amount of transmitter, about 70 pg/g of colon, actually released and bound to receptors. During repetitive stimulation (10/sec), the efflux of NE progressively declines and in 15 min practically ceases, although less than 10% of the amine stores have been released. After resting the colon preparation for 1 hr, the nerve endings again release NE in response to nerve stimulation. These results favor the view that NE is released only from vesicles in the vicinity of the presynaptic membrane and that these vesicles are selectively depleted of the transmitter by repetitive stimulation in the presence of phenoxybenzamine.