A Proposed Dual Neurohumoral Role of Acetylcholine: Its Functions at the Pre- and Post-Synaptic Sites

Koelle, George B.

doi:10.1038/190208a0

Cited by 159 publications

(59 citation statements)

References 27 publications

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“…On the assumption that ACh is present wherever specific ChE is found, they proposed that ACh is present in the gland and acts back on the nerve endings from which it is released, to cause the release of hormones. This action is in keeping with a generalized theory for a presynaptic action of ACh (32). A substance with "acetylcholine-like" activity was reported to be present in extracts of bovine neurohypophysis (55), but one of the authors subsequently attributed this activity to interfering substances (31).…”

Section: Isolated Microvesiclesmentioning

confidence: 53%

Isolated Nerve Endings (Neurosecretosomes) From the Posterior Pituitary

Bindler

LaBella

Sanwal

1967

The Journal of Cell Biology

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Subcellular fractions of the bovine posterior pituitary, including one composed almost exclusively of pinched-off nerve endings (neurosecretosomes), were characterized electron microscopically, hormonally, and enzymically. 15 % of the nerve terminals in the gland were isolated as neurosecretosomes, as estimated from determinations of lactic dehydrogenase, a soluble, cytoplasmic enzyme. Neurosecretosomes were subdivided into three fractions by density-gradient centrifugation. The three subfractions, each shown to be nearly homogeneous populations of neurosecretosomes by means of electron microscopic and enzymic criteria, differed from each other in their vasopressin/oxytocin (VP/OT) ratios. The VP/ OT ratio increased from the lightest to the densest fraction, indicating that VP is localized to denser and OT to lighter neurosecretosomes; similar results have been obtained previously for subfractions of neurosecretory granules (NSG). No morphological differences were apparent in neurosecretosomes among the three subfractions. Although complete separation of VP and OT was not achieved, the findings suggest that VP and OT are each stored in a different species of nerve ending and support the hypothesis that a given neurosecretory cell synthesizes, stores, and secretes only one of the peptide hormones. Microvesicles, 40-80 mg diameter and contained in typical neurosecretory cell terminals, are believed to be degradation products of membrane ghosts of depleted NSG; electron micrographs indicative of this transformation are presented. A fraction rich in microvesicles, but containing some NSG membranes, was prepared by density-gradient centrifugation of an osmolysate of neurosecretosomes. Smaller, apparently nonneurosecretory nerve endings, lacking NSG but filled with small vesicles, are occasionally seen in sections from whole gland. The vesicles in these atypical posterior pituitary nerve endings may be true neurohumor-containing, "synaptic" vesicles.

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Section: Isolated Microvesiclesmentioning

confidence: 53%

Isolated Nerve Endings (Neurosecretosomes) From the Posterior Pituitary

Bindler

LaBella

Sanwal

1967

The Journal of Cell Biology

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“…It may be the membrane of the nerve terminal endings (cf. Volle & Koelle, 1961;Koelle & Koelle, 1959; Koelle, 1961Koelle, , 1962 or the membrane of a more proximal part of the preganglionic nerve terminals (Hubbard, Schmidt & Yokota, 1965). In any case,…”

Section: Discussionmentioning

confidence: 99%

Cholinergic receptors at sympathetic preganglionic nerve terminals

Koketsu¹,

Nishi²

1968

The Journal of Physiology

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SUMMARY1. In the paravertebral sympathetic chain of bullfrogs, some part of the preganglionic nerve located within the ganglion was depolarized transiently when acetylcholine (ACh) was directly applied to the ganglion, particularly in the presence of an anticholinesterase (anti-ChE). The axonal part of the preganglionic nerve, on the other hand, showed no detectable depolarization following direct application of ACh (with anti-ChEs) to the interganglionic nerve trunk.2. The ACh depolarization was markedly depressed by nicotine, and less markedly by (+ )-tubocurarine, whereas it was not affected by atropine. Nicotine, similar to ACh, transiently depolarized only the intraganglionic portion of the presynaptic fibres.3. The action potentials, recorded from the axonal as well as the terminal parts of the preganglionic nerve, showed spike potentials followed by a marked negative after-potential. The negative after-potential was followed by a positive after-potential which was markedly enhanced by repetitive nerve stimulation.4. A slow negative potential followed the positive after-potential in the repetitive responses of the terminal parts of the preganglionic nerve. The slow negative potential was enhanced by anti-ChEs, eliminated by ACh and nicotine, and unaffected by atropine.5. The amplitude of the action potentials of the terminal parts of the preganglionic nerve, and particularly that of the negative after-potential, was significantly depressed during the development of ACh depolarization as well as the slow negative potential, indicating that the two types of slow depolarization originated in the intraganglionic portion of the presynaptic fibres, presumably somewhere near or at the nerve terminals.6. ACh depolarization similar to that observed with bullfrog sympathetic ganglia was observed with rat superior cervical ganglia. The present K. KOKETSU AND S. NISHI experiments provide evidence that a certain part of the preganglionic nerve terminals is depolarized by the action of the transmitter released from their endings.

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“…Koelle (1961Koelle ( , 1962 suggested that the presynaptic effect of ACh is an integral part of the physiology of synaptic transmission. This hypothesis was based, in part, on experiments by Volle & Koelle (1961) which showed that carbachol is a less effective stimulant of the chronically decentralized superior cervical ganglion of the cat than of normally innervated ganglia.…”

Section: Discussionmentioning

confidence: 99%

“…Koelle's (1961) hypothesis predicts that a small amount of exogenously applied ACh should release a large amount of labelled transmitter. This was not so.…”

Section: Transmitter Release By Achmentioning

confidence: 99%

“…The concept that the arrival of an action potential in a presynaptic nerve terminal results in the release of enough transmitter substance to effect synaptic transmission has been challenged by Koelle (1961Koelle ( , 1962). Koelle's hypothesis is that, at cholinergic synapses, a nerve impulse releases too little acetylcholine (ACh) to stimulate the postganglionic cell directly, but enough to prolong the state of depolarization of the presynaptic nerve terminals so that they discharge additional ACh which does effect transmission.…”

Section: Introductionmentioning

confidence: 99%

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The release of acetylcholine by acetylcholine in the cat's superior cervical ganglion

Collier¹,

Katz²

1970

British J Pharmacology

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Summary1 The experiments described in this paper tested the effect of acetylcholine (ACh), carbachol or preganglionic nerve stimulation on the release of ACh from the cat's perfused superior cervical ganglion; radioactive tracer methods were used. 2. When the ganglion's transmitter store of ACh had been labelled, radioactive ACh was released by nerve stimulation (5 Hz for 2 min), but there was no release by ACh (015-15 jg) or by carbachol (1-10 Mig) when these drugs were injected close to the ganglion. Perfusion with low or moderate concentrations of ACh (0-15-5 jug/ml) also failed to release ACh, but high concentrations (15-50 ,tg/ml) released a small amount of labelled material. There was no correlation between ganglion stimulation by ACh and release of radioactivity.3. Ganglion-blocking concentrations of ACh did not reduce the release of ACh during continuous nerve stimulation. 4. When resting (unstimulated) ganglia were perfused with 3H-choline and eserine, the extra ACh synthesized and stored by such ganglia (surplus ACh) was labelled. Preganglionic nerve stimulation (5 Hz for 2 min) did not release surplus ACh, but perfusion with ACh (05-15 pig/ml), or injection of carbachol (0O5-2-5 ytg) did. 5. Surplus ACh released by ACh or by carbachol did not contribute to the ganglion stimulating effect of either drug. 6. It is concluded that the presynaptic effects of ACh are not of physiological importance. IntroductionThe concept that the arrival of an action potential in a presynaptic nerve terminal results in the release of enough transmitter substance to effect synaptic transmission has been challenged by Koelle (1961Koelle ( , 1962). Koelle's hypothesis is that, at cholinergic synapses, a nerve impulse releases too little acetylcholine (ACh) to stimulate the postganglionic cell directly, but enough to prolong the state of depolarization of the presynaptic nerve terminals so that they discharge additional ACh which does effect transmission.This suggestion that there is a positive feed-back mechanism for release implies that exogenously applied ACh, or ACh-like agent, should release transmitter from presynaptic nerve endings, and some evidence has accumulated that this might be

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A Proposed Dual Neurohumoral Role of Acetylcholine: Its Functions at the Pre- and Post-Synaptic Sites

Cited by 159 publications

References 27 publications

Isolated Nerve Endings (Neurosecretosomes) From the Posterior Pituitary

Isolated Nerve Endings (Neurosecretosomes) From the Posterior Pituitary

Cholinergic receptors at sympathetic preganglionic nerve terminals

The release of acetylcholine by acetylcholine in the cat's superior cervical ganglion

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