Acetylcholine Mobilization in a Sympathetic Ganglion in the Presence and Absence of 2‐(4‐Phenylpiperidino)Cyclohexanol (AH5183)

Acetylcholine Mobilization in a Sympathetic Ganglion in the Presence and Absence of... Abstract: The present experiments measured the release of acetylcholine (ACh) by the cat superior cervical ganglia in the presence of, and after exposure to, 2‐(4‐phenylpiperidino)cyclohexanol (AH5183), a compound known to block the uptake of ACh by cholinergic synaptic vesicles. We confirmed that AH5183 blocks evoked ACh release during preganglionic nerve stimulation when approximately 13–14% of the initial ganglial ACh stores had been released; periods of rest in the presence of the drug did not promote recoveiry from the block, but ACh release recovered following the washout of AH5183. ACh was synthesized in AH5183‐treated ganglia, as determined by the synthesis of (3H)ACh from (3H)choline, and this (3H)ACh could be released by stimulation following drug washout. The specific activity of the released ACh matched that of the tissue's ACh. and thus we conclude that ACh synthesized in the presence of AH5183 is as releasable as preexisting ACh stores once the drug is removed. We tested the relative releasability of ACh synthesized during AH5183 exposure (perfusion with (3H)choline) and that synthesized during recovery from the drug's effects (perfusion with (14C)‐choline): the ratio of (3H)ACh to (14C)ACh released by stimulation was similar to the ratio in the tissue. These results suggest that the mobilization of ACh for release by ganglia during recovery from an AH5183‐induced block is independent of the conditions under which the ACh was synthesized. Unlike nerve impulses, black widow spider venom (BWSV) induced the release of ACh from AH5183‐blocked ganglia, even in the drug's continued presence. Venom‐induced release of ACh from AH5183‐treated ganglia was not less than the venom‐induced release from tissues not exposed to AH5183. This effect of BWSV was attributed to the action of the protein, α‐latrotoxin, because an anti‐α‐latrotoxin antiserum blocked the venom's action. ACh synthesized during AH5183 exposure was labelled from (3H)choline, and subsequent treatment with BWSV released (3H)ACh with the same temporal pattern as the release of total ACh. To exclude a nonexocytotic origin for the (3H)ACh released by BWSV, ganglia were preloaded with (3H)diethylhomocholine to form (3H)acetyldiethyl‐homocholine, an ACh analogue excluded from vesicles; the venom did not increase the rate of (3H)acetyldiethylhomo‐choline efflux. It is concluded that a vesicular ACh pool insensitive to the inhibitory action of AH5183 might exist and that this vesicular pool is not mobilized by electrical stimulation to exocytose in the presence of AH5183, but it is by BWSV. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurochemistry Wiley

Acetylcholine Mobilization in a Sympathetic Ganglion in the Presence and Absence of 2‐(4‐Phenylpiperidino)Cyclohexanol (AH5183)

Journal of Neurochemistry, Volume 50 (1) – Jan 1, 1988

Loading next page...
 
/lp/wiley/acetylcholine-mobilization-in-a-sympathetic-ganglion-in-the-presence-EroE0oxckA
Publisher
Wiley
Copyright
Copyright © 1988 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0022-3042
eISSN
1471-4159
DOI
10.1111/j.1471-4159.1988.tb13237.x
Publisher site
See Article on Publisher Site

Abstract

Abstract: The present experiments measured the release of acetylcholine (ACh) by the cat superior cervical ganglia in the presence of, and after exposure to, 2‐(4‐phenylpiperidino)cyclohexanol (AH5183), a compound known to block the uptake of ACh by cholinergic synaptic vesicles. We confirmed that AH5183 blocks evoked ACh release during preganglionic nerve stimulation when approximately 13–14% of the initial ganglial ACh stores had been released; periods of rest in the presence of the drug did not promote recoveiry from the block, but ACh release recovered following the washout of AH5183. ACh was synthesized in AH5183‐treated ganglia, as determined by the synthesis of (3H)ACh from (3H)choline, and this (3H)ACh could be released by stimulation following drug washout. The specific activity of the released ACh matched that of the tissue's ACh. and thus we conclude that ACh synthesized in the presence of AH5183 is as releasable as preexisting ACh stores once the drug is removed. We tested the relative releasability of ACh synthesized during AH5183 exposure (perfusion with (3H)choline) and that synthesized during recovery from the drug's effects (perfusion with (14C)‐choline): the ratio of (3H)ACh to (14C)ACh released by stimulation was similar to the ratio in the tissue. These results suggest that the mobilization of ACh for release by ganglia during recovery from an AH5183‐induced block is independent of the conditions under which the ACh was synthesized. Unlike nerve impulses, black widow spider venom (BWSV) induced the release of ACh from AH5183‐blocked ganglia, even in the drug's continued presence. Venom‐induced release of ACh from AH5183‐treated ganglia was not less than the venom‐induced release from tissues not exposed to AH5183. This effect of BWSV was attributed to the action of the protein, α‐latrotoxin, because an anti‐α‐latrotoxin antiserum blocked the venom's action. ACh synthesized during AH5183 exposure was labelled from (3H)choline, and subsequent treatment with BWSV released (3H)ACh with the same temporal pattern as the release of total ACh. To exclude a nonexocytotic origin for the (3H)ACh released by BWSV, ganglia were preloaded with (3H)diethylhomocholine to form (3H)acetyldiethyl‐homocholine, an ACh analogue excluded from vesicles; the venom did not increase the rate of (3H)acetyldiethylhomo‐choline efflux. It is concluded that a vesicular ACh pool insensitive to the inhibitory action of AH5183 might exist and that this vesicular pool is not mobilized by electrical stimulation to exocytose in the presence of AH5183, but it is by BWSV.

Journal

Journal of NeurochemistryWiley

Published: Jan 1, 1988

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off