Neurotransmitter release in an arterial preparation and the action of alpha-adrenoceptor antagonists.

1 This study examined the potentiating effects of competitive antagonists of the adrenergic alpha2 receptors and of phenoxybenzamine (POB) an irreversible antagonist, on the stimulation-induced efflux of [3H]-noradrenaline in arterial tissue of rabbit. This was done to determine if the lack of concordance of efflux potentiation by antagonists with the expectations of presynaptic negative feedback theory can be attributed to increasingly successful competition from rising perineuronal transmitter concentrations, when stimulation parameters are increased, in the presence of a fixed concentration of competitive antagonist. 2 Tissues were stimulated with a fixed pulse number and frequency, to rule out confounding factors, and major alterations in the concentration of released transmitter were achieved through variations in the pulse duration.

Decrements in per pulse release of norepinephrine, antagonist potentiation of release and presynaptic receptor theory.

In recent decades the theory that amine transmitter release at nerve terminals is routinely regulated through negative feedback systems sensing and responding to the instantaneous perineuronal concentration of previously liberated transmitter has assumed pre-eminence. However, observations indicate a major drop off in per pulse transmitter release when only two or four stimulation pulses are administered, reflecting the unexpectedly prompt operation of feedback inhibition. We explored this quandary in our understanding of control of transmitter release by axonal depolarization versus terminal feedback using isotopic norepinephrine and in vitro slices of rabbit hippocampus.

Rate-independent inhibition of 5-HT release by 5-HT in the somadendritic regions of raphe neurons.

The somadendritic regions of raphe neurons respond to exogenous 5-hydroxytryptamine (5-HT) with an inhibition of spontaneous rate and a consequent reduction in local transmitter release, providing evidence for the operation of negative feedback regulation of spontaneous rate. Experiments were done to determine if a release process for 5-HT might also operate in the somadendritic regions that is independent of negative feedback and rate regulation. Slices of rabbit brain containing medullary or midbrain raphe nuclei, were stimulated in vitro at predetermined frequencies and the efflux of 3H-transmitter determined.

Regarding the unitary theory of agonist and antagonist action at presynaptic adrenoceptors.

1. The linkage between potentiation of field stimulation-induced noradrenaline release and blockade of the presynaptic inhibitory effect of exogenous noradrenaline by a presynaptic antagonist was examined in superfused rabbit aorta preparations. 2.

Rate-independent inhibition by norepinephrine of 5-HT release from the somadendritic region of serotonergic neurons.

Endogenous adrenergic drive regulates the firing rate of serotonergic neurons. However, advocates of feedback theory assert that 5-hydroxytryptamine (5-HT) released in the somatodendritic region of raphe neurons regulates both rate and release of 5-HT. Experiments were done to determine if the somatodendritic region might have receptors for norepinephrine that inhibit release of 5-HT independently of rate, as this would allow for discrete effects of norepinephrine on rate and release, even in the presence of functional feedback by 5-HT.