Is there feedback regulation of neurotransmitter release by autoreceptors?
Neurotransmitter release does not seem to be regulated by neuronal receptors mediating feedback and the mechanism of action of presynaptically active agents is still uncertain. In a recent set of papers [27, 82], experiments were described in which major modifications were made to the amount of neurotransmitter released per impulse, with all other parameters of field stimulation, such as pulse number, voltage and frequency, fully controlled. These studies done with a number of sympathetically innervated tissues give some insight into an antagonist action presynaptically which is independent of the ambient concentration of extracellular transmitter. It appears to involve, instead, the gating mechanisms which control neuronal membrane depolarization and repolarization. It was found that the effects of yohimbine and also of phenoxybenzamine on stimulation-induced efflux appeared to be essentially "all or none". That is, the absolute total release of tritiated transmitter with 100 pulses was elevated to roughly the same dpm value by the presynaptic antagonist at each of the pulse durations between 50 and 1000 microsec, in a variety of test tissues. The declining percentage effect of the antagonist on tritium efflux, as the pulse duration was enlarged between 50 and 1000 microsec, referred to earlier (Fig. 3), was due to rising values for transmitter release in the controls not matched by proportionally similar increases in the antagonist-treated tissues. Values for the amount of transmitter released during stimulation in the presence of yohimbine, at pulse lengths between 50 and 1000 microsec, were all in the range of values achieved in the absence of yohimbine with long pulse lengths (1000-2000 microsec). In other words, prolongation of the pulse duration from 50 to 1000 microsec and the exposure of tissues to a presynaptic antagonist, such as yohimbine or phenoxybenzamine, may involve a common mechanism, and the effects of these two procedures are not additive. In fact, with much prolonged pulse durations (2000-5000 microsec), the presynaptic antagonists are virtually ineffective. It is known that the release of transmitter from sympathetic nerves is directly related to the duration of the action potential. If it is prolonged, the calcium channels stay open longer leading to greater entry of calcium and to an increased release of transmitter [45, 46]. Yohimbine and phenoxybenzamine may prolong the duration of depolarization by indirect modification of the calcium gating mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)
Kalsner
S
S
D000818:Animals; D004558:Electric Stimulation; D005246:Feedback; D006801:Humans; D066298:In Vitro Techniques; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter; D015016:Yohimbine; D009638:Norepinephrine