Possible role of a beta-adrenoceptor in the regulation of noradrenaline release by nerve stimulation through a positive feed-back mechanism.

1 The effects of isoprenaline, propranolol and phentolamine, were studied on tritiated noradrenaline overflow elicited by postganglionic nerve stimulation in guinea-pig isolated atria. 2 Isoprenaline (1.2 times 10-minus 8M) increased while propranolol (1.0 times 10-minus 7M) reduced the overflow of tritiated noradrenaline evoked by nerve stimulation. These effects were less than those of phentolamine (3.1 times 10-minus 6M), which increased by approximately three-fold the overflow of [3H]-noradrenaline elicited by nerve stimulation. 3 Neuronal accumulation of tritiated noradrenaline in guinea-pig atria was not affected by isoprenaline, propranolol or phentolamine at the concentration employed in this study. 4 Isoprenaline (1.2 times 10-minus 8M) induced a positive chronotropic effect of about 80 percent of the maximum. On the other hand, propranolol produced a shift to the right in the frequency-response curve to nerve stimulation and in the concentration-response curve to exogenous noradrenaline in guinea-pig atria. 5 In the isolated nictitating membrane of the cat, the frequency-response curve to nerve stimulation was not modified by propranolol, while in the presence of 3.9 times 10-minus 6M of N,-2-(2,6-dimethylphenoxy)propyl-N,N,N-trimethylammonium (beta-methyl-TM 10) there was a shift to the right and a depression of slope. Neither propranolol nor beta-methyl-TM 10 affected responses to exogenous noradrenaline. 6. The effects of isoprenaline and of propranolol on transmitter release are compatible with the view that in addition to the presynaptic negative feed-back mechanism for noradrenaline release by nerve stimulation mediated via alpha-adrenoceptors a positive feed-back mechanism exists in adrenergic nerve endings which is triggered through the activation of presynaptic beta-adrenoceptors.