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Biomedical subjects

B Collier

Publications and source records attributed to B Collier.

At least 55 records · Page 3Linked to original sources
PubMed1986

Acetylcholine synthesis and release by a sympathetic ganglion in the presence of 2-(4-phenylpiperidino) cyclohexanol (AH5183).

These experiments measured the release and the synthesis of acetylcholine (ACh) by cat sympathetic ganglia in the presence of 2-(4-phenylpiperidino) cyclohexanol (AH5183), an agent that blocks the uptake of ACh into synaptic vesicles. Evoked transmitter release during short periods of preganglionic nerve stimulation was not affected by AH5183, but release during prolonged stimulation was not maintained in the drug's presence, whereas it was in the drug's absence. The amount of ACh releasable by nerve impulses in the presence of AH5183 was 194 +/- 10 pmol, which represented 14 +/- 1% of the tissue ACh store. The effect of AH5183 on ACh release was not well antagonized by 4-aminopyridine (4-AP), and not associated with inhibition of stimulation-induced calcium accumulation by nerve terminals. It is concluded that AH5183 blocks ACh release indirectly, and that the proportion of stored ACh releasable in the compound's presence represents transmitter in synaptic vesicles available to the release mechanism. The synthesis of ACh during 30 min preganglionic stimulation in the presence of AH5183 was 2,448 +/- 51 pmol and in its absence it was 2,547 +/- 273 pmol. Thus, as the drug decreased ACh release it increased tissue content. The increase in tissue content of ACh in the presence of AH5183 was not evident in resting ganglia; it was evident in stimulated ganglia whether or not tissue cholinesterase was inhibited; it was increased by 4-AP and reduced by divalent cation changes expected to decrease calcium influx during nerve terminal depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗
PubMed1986

Choline analogues: their use in studies of acetylcholine synthesis, storage, and release.

The objective of this article is to illustrate how choline analogues might provide insight into mechanisms that regulate the synthesis, storage, and release of acetylcholine (ACh). Studies with false neurotransmitters provide information about the origin of releasable transmitter. Thus, false esters that distribute like ACh to vesicle-bound stores are as releasable as is ACh, but esters that poorly localize to synaptic vesicles are poorly releasable. Studies of choline analogue uptake provide information about the structural specificity of that transport process and, also, show that choline uptake is regulated in response to activity. Thus, stimuli that normally release transmitter increase the rate of choline transport, presumably to provide more precursor for ACh synthesis. However, the relationship between precursor delivery and product formed can be dissociated, suggesting that some factor in addition to choline delivery is involved in ACh synthesis regulation. Studies with a compound (AH5183), which inhibits ACh uptake by synaptic vesicles, provide information about the relationship of ACh stores and releasable transmitter. In the presence of AH5183 some 15% of nerve terminal ACh is released in response to nerve impulses, suggesting the existence of a small population of vesicles that contain readily releasable ACh. In presence of AH5183, ACh synthesis is activated even when ACh release is depressed, showing that transmitter synthesis can be regulated by some factor other than nerve terminal ACh levels.

Acetylation↗
PubMed1977

The effect of preganglionic nerve stimulation on the accumulation of certain analogues of choline by a sympathetic ganglion.

1. Cat superior cervical ganglia were perfused with a Krebs solution containing 10(-6) M [3H]homocholine (2-hydroxypropyl-trimethylammonium) or 10(-5) M [14C]triethylcholine (2-hydroxyethyl-triethylammonium). Preganglionic nerve stimulation (20 Hz) increased the accumulation of homocholine (3-2-fold) and of triethylcholine (2-1-fold). This increased accumulation during stimulation was not the result of increased metabolism. 2. The increased accumulation of homocholine or triethylcholine induced by pregnaglionic nerve stimulation was not reduced by tubocurarine or by atropine, but it was blocked by choline and by hemicholinium. These results suggested that preganglionic nerve stimulation increased choline analogue accumulation into cholinergic nerve terminals. 3. The increased accumulation of homocholine or of triethylcholine induced by preganglionic nerve stimulation was reduced when the Ca2+ concentration was reduced and was abolished in the absence of Ca2+. However, changes in the Mg2+ concentration which depressed acetylcholine (ACh) release by amounts comparable to those induced by altered Ca2+ concentrations did not alter the uptake of homocholine or triethylcholine. It is concluded that the uptake of choline analogues is not regulated by transmitter release but that stimulation increases the uptake of the choline analogues by a Ca2+-dependent mechanism. 4. The accumulation of ACh by ganglia perfused with a Krebs solution containing choline and high MgSO4 (18 mM) was measured. The ACh content of these ganglia did not increase, although choline transport presumably exceeded that necessary for ACh synthesis to replace released ACh. It is concluded that choline transport does not limit ACh synthesis in ganglia.

Acetylcholine↗
PubMed1977

Action of a beta-bungarotoxin on autonomic ganglia and adrenergic neurotransmission.

A beta-bungarotoxin was isolated from the venom of Bungarus multicinctus by column chromatography on Sephadex G-50 and SP-Sephadex. The toxin produced presynaptic effects on neuromuscular transmission with characteristics similar to those described by others. In a sympathetic ganglion, the toxin increased spontaneous acetylcholine (ACh) release and decreased ACh release evoked by preganglionic nerve stimulation. The toxin did not block the response of isolated ileum to cholinergic nerve stimulation, did not block the release of noradrenaline from the adrenergic nerve terminals of a nictitating membrane preparation, and did not alter the responses of smooth and cardiac muscle preparations to noradrenaline. It is suggested that the specificity of beta-bungarotoxin for certain nerve terminals is related either to selective binding of the toxin or to the selective presence of a necessary substrate for its action. An attempt to show selective binding of 125I-toxin to cholinergic nerve terminals in skeletal muscle was not successful.

Acetylcholine↗
PubMed1977

The effects of neomycin upon transmitter release and action.

These experiments were designed to determine the site and mechanism of action of neomycin on cholinergic transmission. These agents depressed the response of rat diaphragm preparations to phrenic nerve stimulation and to injected acetylcholine (ACh); however, equi-effective neuromuscular blocking concentrations of neomycin (6 x 10(-4) M), streptomycin (1.2 x 10(-3) M) or d-tubocurarine (6.5 x 10(-7) M) reduced the muscle response to injected ACh to 54,27 and 15% of control, respectively, suggesting that neomycin and streptomycin have a presynaptic effect. This finding was confirmed by measuring ACh release from the diaphragm during phrenic nerve stimulation; neomycin (6x10(-4) M) and streptomycin (1.2 x 10(-4) M) depressed ACh release to 29 and 41% of control, respectively. In the cat superior cervical ganglion neomycin (2 x 10(-3) M) blocked ganglionic transmission, did not reduce the response of ganglion cells to injected nicotine and depressed ACh release during preganglionic nerve stimulation to 61% of control in normal Ca++ (2.5 mM) medium and to less than 10% of control in low Ca++ (0.5 mM) medium. The increased accululation of 45Ca induced in rat isolated ganglia by preganglionic nerve stimulation was not changed by d-tubocurarine (2 x 10(-4) M), but was abolished by neomycin (2 x10(-3) M). It is concluded that neomycin blocks ACh release by blocking the influx of Ca++ necessary for transmitter release. This conclusion suggested that neomycin should block noradrenaline release, and this was shown using the anococcygeus preparation from the rat.

Acetylcholine↗
PubMed1976

The site of the neuromuscular block produced by polymyxin B and rolitetracycline.

The site of neuromuscular blockade induced by polymyxin B and rolitetracycline was studied on isolated nerve and nerve-muscle preparations. Polymyxin B (1.8 X 10(-4) M) was equipotent to lidocaine as a local anaesthetic on a frog desheathed nerve preparation, while rolitetracycline (up to 3.6 X 10(-3)M) had no local anaesthetic effect. Polymyxin B (6 X 10(-5) M) and rolitetracycline (7 X 10(-4) M) blocked by 50% the response of rat diaphragm induced by phrenic nerve stimulation, but did not decrease the amount of acetylcholine (ACh) released from this preparation during nerve stimulation. Both antibiotics depressed the response of the rat diaphragm to inject ACh, and this response was more sensitive to inhibition by the drugs than was the response to nerve stimulation. With rolitetracycline, a concentration that blocked the response to nerve stimulation by 50% inhibited the response to injected ACh by 85%, and this relationship was similar to that with d-tubocurarine; however, polymyxin B was relatively more effective than d-tubocurarine in inhibiting the effect of ACh. Polymyxin B (1-1.5 X 10(-4) M) but not rolitetracycline (1 X 10(-3) M) depressed the response of the diaphragm to direct muscle stimulation. It is concluded that polymyxin B and rolitetracycline block neuromuscular transmission predominatly by an effect to depress the muscle's sensitivity to ACh; polymyxin B probably acts by an effect similar to that of local anaesthetics, while rolitetracycline probably acts by an effect similar to that of d-tubocurarine.

Acetylcholine↗
PubMed1976

Characterization of the neuromuscular block produced by clindamycin and lincomycin.

The site of neuromuscular blockade induced by clindamycin and lincomycin was studied on isolated nerve and nerve-muscle preparations. Clindamycin (3.6 X 10(-3) M) but not lincomycin (up to 1.5 X 10(-2) M) had a local anaesthetic effect on a frog desheathed nerve preparation. Clindamycin (8 X 10(-4) M) and lincomycin (4 X 10(-3) M) depressed the response of the rat diaphragm to nerve stimulation and to direct muscle stimulation in parallel. This indicated that the predominant neuromuscular blocking effect of these antibiotics was due to an effect on the muscle. Clindamycin was fivefold more potent than lincomycin in this effect, and the unionized form of both drugs was the active form. Lincomycin (4 X 10(-3) M) but not clindamycin (8 X 10(-4) M) also had some depressant effect on nerve-muscle transmission as indicated by the interaction of the effects of the antibiotics and d-tubocurarine. The significance of these findings is discussed in relation to the acute clinical toxicity of these antibiotics.

Animals↗