Comparison between the effects produced by chronic denervation and by cocaine on the sensitivity to,and on the disposition of,noradrenaline in isolated spleen strips

Summary A comparison was made between the effects of cocaine and denervation on the sensitivity to, on the rate of inactivation of, and on the roles played by iproniazid and tropolone in the inactivation of noradrenaline by cat spleen strips. For studying the rate of inactivation of noradrenaline the oil immersion technique was used. Cocaine was used in four different concentrations. In all concentrations did it enhance the sensitivity to noradrenaline. When cocaine was used in concentrations of 10 and 50×10^–6 M, the enhancement was significantly higher than that caused by denervation (11.61 and 14.81 vs. 6.42, respectively: p<0.001). Since denervation produces an enhancement of the effect of noradrenaline which is smaller than that caused by cocaine, the blockade of neuronal uptake cannot fully account for all supersensitivity induced by cocaine. On the other hand, cocaine produces no further enhancement of the effect of noradrenaline in denervated strips. It is assumed that cocaine acts in normal (control) preparations by two mechanisms: 1. blockade of neuronal uptake accounting for an enhancement like that caused by denervation (about 6 times); 2. facilitation of the action of noradrenaline by interference with a hypothetical postjunctional structure which depends on the presence of intact adrenergic nerves and which accounts for the remaining degree of enhancement (about 2 times).Strips treated with cocaine (50×10^–6 M) required for half-relaxation 7.42 times the time of the controls, whereas denervated strips only required 4.84 times the control time. On the other hand in denervated strips cocaine (50×10^–6 M) produced a further 1.55-fold prolongation of the half-relaxation time. Thus, the effect of cocaine on this parameter is concluded to be due primarily to blockade of neuronal uptake and secondarily to another factor, which could be related to uptake₂.The influence of cocaine and denervation on the role played by iproniazid and tropolone on the inactivation of noradrenaline was not significantly different; apparently, in this preparation, the monoamine oxidase involved in terminating the action of noradrenaline is predominantly if not entirely situated intraneuronally, whereas catechol-O-methyltransferase seems to be situated intra- and extraneuronally almost in equal proportions.