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R L Buyukuysal

Publications and source records attributed to R L Buyukuysal.

8 recordsLinked to original sources
PubMed1995

3,4-Diaminopyridine and choline increase in vivo acetylcholine release in rat striatum.

We investigated the effects of choline, 3,4-diaminopyridine and their combination on acetylcholine release from the corpus striatum of freely moving rats which were treated or not with atropine. Intraperitoneal administration of choline or intrastriatal administration of 3,4-diaminopyridine increased acetylcholine levels in striatal dialysates in a dose-dependent manner. When 3,4-diaminopyridine treatment was combined with choline, the observed effect was considerably greater than the sum of the increases produced by choline or 3,4-diaminopyridine alone. Administration of atropine (1 microM) in the dialysing medium was also found to be effective to stimulate striatal acetylcholine levels. 3,4-Diaminopyridine did not affect acetylcholine levels under these conditions. Whereas the choline-induced increase in acetylcholine release was significantly potentiated by atropine, co-administration of 3,4-diaminopyridine with choline failed to produce a further significant increase in the presence of atropine. These results suggest that a highly effective means for increasing acetylcholine release involves two concurrent treatments that increase neuronal choline levels and inhibition of the negative feedback modulation of acetylcholine release.

4-Aminopyridine↗
PubMed1992

N-methyl-D-aspartate increases acetylcholine release from rat striatum and cortex: its effect is augmented by choline.

We examined the effects of N-methyl-D-aspartate (NMDA), a glutamate agonist, and of glutamate itself, on acetylcholine (ACh) release from superfused rat striatal slices. In a Mg(++)-free medium, NMDA (32-1000 microM) as well as glutamate (1 mM) increased basal ACh release by 35 to 100% (all indicated differences, P less than .05), without altering tissue ACh or choline contents. This augmentation was blocked by Mg++ (1.2 mM) or by MK-801 (10 microM). Electrical stimulation (15 Hz, 75 mA) increased ACh release 9-fold (from 400 to 3660 pmol/mg of protein): this was enhanced (to 4850 pmol/mg of protein) by NMDA (100 microM). ACh levels in stimulated slices fell by 50 or 65% depending on the absence or presence of NMDA. The addition of choline (40 microM) increased ACh release both basally (570 pmol/mg of protein) and with electrical stimulation (6900 pmol/mg of protein). In stimulated slices choline acted synergistically with NMDA, raising ACh release to 10,520 pmol/mg of protein. The presence of choline also blocked the fall in tissue ACh. No treatment affected tissue phospholipid or protein levels. NMDA (32-320 microM) also augmented basal ACh release from cortical but not hippocampal slices. Choline efflux from striatal and cortical (but not hippocampal) slices decreased by 34 to 50% in Mg(++)-free medium. These data indicate that NMDA-like drugs may be useful, particularly in combination with choline, to enhance striatal and cortical cholinergic activity. ACh release from rat hippocampus apparently is not affected by NMDA receptors.

Acetylcholine↗
PubMed1991

Interactions of 3,4-diaminopyridine and choline in stimulating acetylcholine release and protecting membrane phospholipids.

We investigated the effects of 3,4-DAP on ACh release from rat striatal slices superfused with or without choline, at rest and during electrical stimulation. In a choline-free medium, 3,4-DAP increased basal and stimulated ACh release while lowering the net efflux of choline; thus while the sum of ACh plus choline released remained constant, the ratio of released ACh to that of choline was increased. The drug failed to affect tissue ACh, choline or membrane phospholipid levels (including those of phosphatidylcholine). In a choline-containing medium, 3,4-DAP potentiated the enhancement by choline of both basal and electrically stimulated ACh release. Electrical stimulation alone increased ACh release from the slices without altering choline efflux or depleting tissue choline or ACh stores; however, this treatment did deplete membranes of phosphatidylcholine and of other major phospholipids. Superfusion of the slices with 3,4-DAP protected the slices from stimulation-induced phospholipid depletion. Calcium-dependent activation of high-affinity choline uptake may underlie the observed effects of 3,4-DAP.

4-Aminopyridine↗
PubMed1990

4-Aminopyridine increases acetylcholine release without diminishing membrane phosphatidylcholine.

4-Aminopyridine (10(-4)-10(-5) M) increased severalfold the release of acetylcholine from rat striatal slices superfused with an eserine-containing, choline-free medium, and caused stoichiometric decreases in the release of choline. It had no effect on tissue acetylcholine and choline levels. Electrical stimulation of the striatal slices increased acetylcholine release without affecting that of choline. Superfusion of the stimulated slices with 4-aminopyridine decreased choline release and increased the ratio of acetylcholine to choline in superfusates. As shown previously, electrical stimulation of the striatal slices decreased their contents of phospholipids, principally phosphatidylcholine; 4-aminopyridine fully protected against these membrane changes. In synaptosomal preparations, 4-aminopyridine was found to enhance the high-affinity uptake of [14C]choline and its conversion to [14C]acetylcholine. This effect on choline uptake may underlie 4-aminopyridine's ability to enhance acetylcholine release in the absence of supplemental choline while suppressing the "autocannibalism" of membrane phospholipids.

4-Aminopyridine↗
PubMed1989

Tetrahydroaminoacridine but not 4-aminopyridine inhibits high-affinity choline uptake in striatal and hippocampal synaptosomes.

We have compared the effects of tetrahydroaminoacridine (THA), 4-aminopyridine (4-AP) and tetraethylammonium (TEA) on high affinity choline uptake and the release of newly synthesized acetylcholine (ACh) from striatal and hippocampal synaptosomes, and on choline acetyltransferase (ChAT) activity in rat striatal synaptosomes. Incubation of the striatal synaptosomes with various THA concentrations (5-100 microM) caused a concentration-dependent inhibition in their accumulation of soluble 14C-labeled compounds ([14C]choline and [14C]ACh); at concentrations of 50 microM or greater the THA also completely suppressed the release of newly synthesized [14C]ACh. 4-AP slightly but significantly decreased the accumulation of the [14C]ACh in the striatal synaptosomes, without affecting that of [14C]choline, but markedly increased the release of [14C]ACh into the medium; hence the drug stimulated net choline uptake (by 19, 20 and 31%, respectively, in the presence of 5, 50 and 100 microM concentrations). Like THA, but not 4-AP, TEA decreased both the accumulation of soluble 14C-compounds in the striatal synaptosomes and the release of newly synthesized [14C]ACh. Similar effects of THA and 4-AP on HACU and the release of [14C]ACh were also observed when hippocampal synaptosomes were used. THA and 4-AP are structurally similar, and share with TEA the ability to block certain potassium channels. Present data show that, in spite of these similarities, these compounds produce opposite effects on net choline uptake by striatal and hippocampal synaptosomes.

4-Aminopyridine↗
PubMed1988

Choline as an agonist: determination of its agonistic potency on cholinergic receptors.

These experiments examined the potency of choline as a cholinergic agonist at both muscarinic and nicotinic receptors in rat brain and peripheral tissues. Choline stimulated the contraction of isolated smooth muscle preparations of the stomach fundus, urinary bladder and trachea and reduced the frequency of spontaneous contractions of the right atrium at high micromolar and low millimolar concentrations. The potency of choline to elicit a biological response varied markedly among these tissues; EC50 values ranged between 0.41 mM in the fundus to 14.45 mM in the atrium. Choline also displaced [3H]quinuclidinyl benzilate binding in a concentration-dependent manner although, again, its potency varied among different brain regions (Ki = 1.2 to 3.5 mM) and peripheral tissues (Ki = 0.28 to 3.00 mM). Choline exhibited a comparable affinity for nicotinic receptors. It stimulated catecholamine release from the vascularly perfused adrenal gland (EC50 = 1.3 mM) and displaced L-[3H]nicotine binding to membrane preparations of brain and peripheral tissues (Ki = 0.38 to 1.17 mM). However, the concentration of choline required to bind to cholinergic receptors in most tissues was considerably higher than serum levels either in controls (8-13 microM) or following the administration of choline chloride (200 microM). These results clearly demonstrate that choline is a weak cholinergic agonist. Its potency is too low to account for the central nervous system effects produced by choline administration, although the direct activation of cholinergic receptors in several peripheral tissues may explain some of its side effects.

Acetylcholine↗