Vascular responses and noradrenaline overflows in the isolated blood-perfused cat spleen: some effects of cocaine, normetanephrine and -blocking agents.

1. Vascular responses and noradrenaline overflows have been studied in the isolated blood-perfused cat spleen in response to electrical stimulation of the splenic nerve with trains of 200 supramaximal pulses at a frequency of 10 Hz given at 10 min intervals.2. In the absence of blocking agents the spleen gave well-defined responses and a mean maximum overflow of 436 +/- 96 pg noradrenaline per stimulus (n = 4) at the third train of stimuli.3. Cocaine (2 x 10(-5)M) increased the response nearly threefold and raised the overflow to 840 +/- 131 pg/stim (n = 4). At later stimulations the responses remained stable, but the overflows rose progressively to 1076 +/- 51 pg/stim after five trains of stimuli.4. Normetanephrine (10(-4)M) had no significant effect on response, but elevated the overflow to a mean maximum of 868 +/- 169 pg/stim (n = 4).5. Cocaine (2 x 10(-5)M) and normetanephrine (10(-4)M) given together increased the response by a factor of 6.5 and raised the overflow to 1258 +/- 247 pg/stim (n = 4).6. Hydergine (approx. 10(-5)M) almost completely abolished the response and raised the overflow to 859 +/- 173 pg/stim (n = 4).7. Cocaine (2 x 10(-5)M), normetanephrine (10(-4)M) and hydergine (approx. 10(-5)M) given in combination abolished the response and raised the overflow to 4089 +/- 1148 pg/stim (n = 4).8. Phenoxybenzamine (10(-4)M) abolished the response and elevated the overflow to 4215 +/- 738 pg/stim (n = 4).9. These results are interpreted in terms of selective and combined block of ;uptake I', ;uptake II' and alpha-adrenergic receptors. Facilitation of transmitter release by alpha-blocking drugs, and the possible existence of an uptake process associated with the alpha-receptors are discussed.