• Archives of Pharmacal Research
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• v.19 no.6
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• pp.520-528
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• 1996

The involvement of the cyclic AMP (cAMP) effector system in the release of endogenous dopamine and acetylcholine from the rat neostriatum was assessed. Forskolin, an activator of adenylate cyclase, was used to enhance cAMP production, and the consequence of this enhancement on the spontaneous and potassium stimulated release of dopamine and acetylcholine was evaluated. Neostriatal slices were prepared from Fischer 344 rats and after a preincubation period the release of each endogenous neurotransmitter was measured from the same slice preparation. To measure acetylcholine release the slice acetylcholinesterase (AChE) activity was inhibited with physostigmine, but the release from slices with intact AChE activity was also determined (choline, instead of acetylcholine was detected in the medium). Under both conditions forskolin induced a significant dose-dependent increase in the potassium-evoked release of dopamine. In the same tissue preparations the release of neither acetylcholine (AChE inhibited) nor choline (AChE intact) was affected by forskolin. The results indicate that the CAMP second messenger system might be involved in neuronal mechanisms that enhance neostriatal dopamine release, but stimulation of this second messenger by forskolin does not further enhance neostriatal acetylcholine release.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.179-179
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• 1996

The involvement of the cyclic AMP (cAMP) effector system in the release of endogenous dopamine and acetylcholine from the rat neostriatum was assessed. Forskolin, an activator of adenylate cyclase, was used to enhance CAMP production, and the consequence of this enhancement on the spontaneous and potassium stimulated release of dopamine and acetylcholine was evaluated. Neostriatal slices were prepared from Fischer 344 rats and after a preincubation period the release of each endogenous neurotransmitter was measured from the same slice preparation. To measure acetylcholine release the slice acetylcholinesterase (AChE) activity was inhibited with physostigmine, but the release from slices with intact AChE activity was also determined (choline, instead of acetylcholine was detected in the medium). Under both conditions forskolin induced a significant dose-dependent increase in the potassium-evoked release of dopamine. In the same tissue preparations the release of neither acetylcholine (AChE inhibited) nor choline (AChE intact) was affected by forskolin. The results indicate that the cAMP second messenger system is involved ill neuronal mechanisms that enhance neuronal dopamine release, but stimulation of this second messenger by forskolin does not further enhance neostriatal acetylcholine release.

• The Korean Journal of Pharmacology
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• v.19 no.1
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• pp.71-76
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• 1983

Aminoglycoside antibiotics are reported to enhance the amylase release from isolated slices of pancreas in vitro and the mode of action of aminoglycosides on amylase release is considered different from those of acetylcholine or cholecystokinin(CCK), i.e., electronmicroscopically intact zymogen granules are appeared in the lumen of pancreatic acini by treatment of aminoglycosides. It is known that atropine blocks the secretagogue effect of acetylcholine, and phenoxybenzamine is reported to block the effects of CCK or its analogue caerulein. Present study was undertaken to investigate the mode of action of aminoglycosides on the amylase release using atropine, phenoxybenzamine and propranolol as a membrane stabilizing agent in slices of chicken pancreas. The results are summarized as follows : 1) Streptomycin and kanamycin increased the amylase release significantly from slices of chicken pancreas. 2) The effect of streptomycin was inhibited by atropine but not by phenoxybenzamine or propranolol. 3) The amylase release by acetylcholine was blocked by atropine tut the effect of cholecystokinin octapeptide(CCK-8) was not influenced by atropine, phenoxybenzamine or propranolol. 4) Pretreatment of streptomycin enhanced the secretagogue effect of acetylcholine or CCK-8. From these results it is suggested that amylase releasing effects of aminoglycosides are mediated in part by cholinergic stimulation and in part by membrane alteration and these effects are enhanced by acetylcholine or cholecystokinin.

• The Korean Journal of Pharmacology
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• v.30 no.2
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• pp.145-152
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• 1994

As it has been reported that the depolarization induced acetylcholine(ACh) release is modulated by activation of presynaptic $A_1-adenosine$ heteroreceptor and various lines of evidence indicate the $A_2-receptor$ is present In hippocampus, this study was undertaken to delineate the role of adenosine receptors on hippocampal ACh release. Slices from the rat hippocampus were equilibrated with $[^3H]-choline$ and the release of the labelled product, $[^3H]-ACh$, which evoked by electrical stimulation(3 Hz, $5\;Vcm^{-1}$, 2 ms, rectangular pulses) was measured, and the influence of various agents on the evoked tritium outflow was Investigated. Adenosine$(0.3{\sim}100\;{\mu}M)$ and CPA$(0.1{\sim}30\;{\mu}M)$ decreased the $[^3H]-ACh$ release in a dose-dependent manner without changing the basal rate of release. DPCPX$(1{\sim}10\;{\mu}M)$, a selective $A_1-receptor$, antagonist, increased the $[^3H]-ACh$ release in a dose related fashion with slight increase of basal tritium release. And the effects of adenosine and CPA were significantly inhibited by $DPCPX(2\;{\mu}M)$ treatment. CPCA, a specific $A_2-agonist$, in concentration ranging from 0.3 to 30 ${\mu}M$, decreased the evoked tritium outflow, and these effects were also abolished by $DPCPX(2\;{\mu}M)$ treatment. But the CPCA effects were not affected by $DMPX(2\;{\mu}M)$, a specific Aa-antagonist, treatment. However, CGS 21680c, a recently introduced potent $A_2-agonist$, in concentration ranging from 0.1 to $10{\mu}M$, did not alter the evoked tritium outflow. These results indicate that the decrement of the evoked ACh release by adenosine is mediated by $A_1-heteroreceptor$, but $A_2-adenosine$ receptor is not involved in ACh release in the rat hippocampus.

• Biomolecules & Therapeutics
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• v.30 no.1
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• pp.90-97
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• 2022

Recently, increasing evidence suggests that neuroinflammation may be a critical factor in the development of Parkinson's disease (PD) in addition to the ratio of acetylcholine/dopamine because dopaminergic neurons are particularly vulnerable to inflammatory attack. In this study, we investigated whether botulinum neurotoxin A (BoNT-A) was effective for the treatment of PD through its anti-neuroinflammatory effects and the modulation of acetylcholine and dopamine release. We found that BoNT-A ameliorated MPTP and 6-OHDA-induced PD progression, reduced acetylcholine release, levels of IL-1β, IL-6 and TNF-α as well as GFAP expression, but enhanced dopamine release and tyrosine hydroxylase expression. These results indicated that BoNT-A had beneficial effects on MPTP or 6-OHDA-induced PD-like behavior impairments via its anti-neuroinflammation properties, recovering dopamine, and reducing acetylcholine release.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.6
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• pp.301-305
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• 2004

This study examined the effects of N-methyl-D-aspartate (NMDA), ${\alpha}-amino$-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate on basal and electrically-evoked release of acetylcholine (ACh) from the rat hippocampal and striatal slices which were preincubated with $[^3H]choline$. Unexpectedly, the basal and evoked ACh release were not affected at all by the treatment with NMDA $(3{\sim}100{\mu}M)$, AMPA $(1{\sim}100{\mu}M)$ or kainate $(1{\sim}100{\mu}M)$ in hippocampal slices. However, in striatal slices, under the $Mg^{2+}-free$ medium, $30{\mu}M$ NMDA increased the basal ACh release with significant decrease of the electrically-evoked releases. The treatment with $1{\mu}M MK-801 not only reversed the $30{\mu}M$ NMDA-induced decrease of the evoked ACh release, but also attenuated the facilitatory effect of $30\;{\mu}M$ NMDA on the basal ACh release. The treatment with either $30\;{\mu}M$ AMPA or $100\;{\mu}M$ kainate increased the basal ACh release without any effects on the evoked release. The treatment with $10{\mu}M$ NBQX abolished the AMPA- or kainate-induced increase of the basal ACh release. Interestingly, NBQX significantly attenuated the evoked release when it was treated with AMPA, although it did not affect the evoked release alone without AMPA. These observations demonstrate that in hippocampal slices, ionotropic glutamate receptors do not modulate the ACh release in cholinergic terminals, whereas in striatal slices, activations of ionotropic glutamate receptors increase the basal ACh release though NMDA may decrease the electrically-evoked ACh release.

• Natural Product Sciences
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• v.10 no.5
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• pp.240-243
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• 2004

In the present study, the alcoholic extract of Terminalia arjuna (TA) and Arjunolic acid (AA) were studied fur its anti-asthmatic and anaphylactic activity. Treatment with TA (250 & 500 mg/kg) and AA (50 & 100 mg/kg) has shown significant protection against mast cell disruption in rats induced by compound 48/80. TA and AA also protected the guinea pig against histamine as well as acetylcholine induced bronchospasm. Both TA & AA exhibited better protection against histamine release than against acetylcholine release. Anti-asthmatic and anaphylactic activity may be possibly due to membrane stabilizing potential and inhibition of antigen induced histamine and acetylcholine release.

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.89-97
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• 1991

As it has been reported that the depolarization-induced release of acetylcholine(ACh) is diminished by activation of presynaptic muscarinic autoreceptor in rabbit hippocampus and various lines of evidence indicate the involvement of adenylate cyclase system in ACh release, it was attempted to delineate the role of cAMP in the muscarinic autoreceptor-mediated control of ACh release. Slices and synaptosomal preparations from rabbit hippocampus were incubated with $[^3H]-choline$ and the release of the labelled products was evoked either by electrical stimulation or by $high-K^+$, and the influence of various agents on the evoked tritium release was investigated. Forskolin, a specific adenylate cyclase activator, in concentrations ranging from $0.1\;to\;30\;{\mu}M$, increased the $[^3H]-ACh$ release in a dose-dependent manner and also dbcAMP increased the tritium outflow. The responses to oxotremorine, a specific muscarinic agonist, were characterized by decrement of ACh release in dose range of $0.1-30\;{\mu}M$, and the oxotremorine effects were inhibited either by forskolin or by atropine. Glibenclamide, a specific $K^+-channel$ inhibitor, in concentration of $1{\sim}10\;{\mu}M$, decreased the evoked ACh release slightly and inhibited the enhancing effect of evoked ACh-release of a large dose$(10\;{\mu}M)$ of forskolin. These results indicate that the cAMP might play a role in the muscarinic ACh receptor-mediated control of ACh rlease in the rabbit hippocampus and suggest that certain potassium currents may also be participated in the post-receptor mechanism of ACh release.

• The Korean Journal of Pharmacology
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• v.32 no.2
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• pp.127-138
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• 1996

The effects of adenosine analogues on the electrically-evoked acetylcholine(ACh) release and the influence of ischemia on the effects were studied in the rat hippocampus. Slices from the rat hippocampus were equilibrated with $0.1{\mu}M$ $[^3H]-choline$ and the release of the labelled product, $[^3H]-ACh$, was evoked by electrical stimulation(3 Hz, 2 ms, 5 $VCm^{-1}$ and rectangular pulses for 2 min), and the influence of various agents on the evoked tritiumoutflow was investigated. Ischemia(10 min with 95% $N_2$ + 5% $CO_2$) increased both the basal and evoked ACh release. These increases were abolished by glucose addition into the superfused medium, and they significantly inhibited either by 0.1 & $0.3{\mu}M$ TTX pretreatment or by removing $Ca^{++}$ in the medium. MK-801($1{\sim}10{\mu}M$), a specific NMDA receptor antagonist, and glibenclamide $(1{\mu}M)$, a $K^+-channel$ inhibitor, did not alter the evoked ACh release and nor did they affect the ischemia-induced increases In ACh release. However, polymyxin B(0.03 mg), a specific protein kinase C inhibitor, significantly inhibited the effects of ischemia on the evoked ACh release. Adenosine and $N^6-cyclopentyladenosine$ decreased the ACh release in a dose dependent manner in ischemic condition, though the magnitude of inhibition was far less than those in normal(normoxic) condition. However, the treatment with $5{\mu}M$ DPCPX, a potent $A_1-adenosine$ receptor antagonist, potentiated the ischemia-effect. These results indicate that the evoked-ACh release is potentiated by ischemia, and this process being most probably mediated by protein kinase C, and that the decreased effect of ACh release mediated by $A_1-adenosine$ receptor is significantly inhibited in ischemic state.

• The Korean Journal of Pharmacology
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• v.27 no.2
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• pp.125-133
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• 1991

In the isolated rabbit mesenteric artery denuded of endothelium, we characterized the identity of the A23187-induced endothelium-dependent relaxing factor (EDRF) released from the endothelium of rabbit aorta, which is distinct from that of acetylcholine-induced relaxing factor. In the normal physiological salt solution (PSS), the dose-response curves to A23187 and acetylcholine were overlapped together. Their effects were also inhibited by methylene blue. Upon application of hypoxanthine and xanthine oxidase into the bath, the phenylephrine-induced precontraction was transiently increased followed by the sustained relaxation. During the burst of hypoxanthine-xanthine oxidase reaction, the $Ca^{++}$ ionophore, A23187 but not acetylcholine was able to cause an immediate relaxation. However, A23187-induced relaxation was not manifested when precontracted by 50 mM $K^+-PSS$. Nevertheless, in the presence of superoxide dismutase, A23187 could produce an immediate relaxation without accompanying the transient contraction as acetylcholine did during the hypoxanthine-xanthine oxidase reaction. On the other hand, acetylcholine-induced relaxation was more sensitively inhibited by phorbol 12-myristate 13-acetate (PMA) than A23187-induced relaxation. Endothelium-independent relaxation to sodium nitroprusside was not affected by PMA. Based on these results it is suggested that both A23187 and acetylcholine cause the methylene blue-inhibitable endothelium-dependent relaxation, and in addition, A23187 may release a stable EDRF which is resistant to superoxide anion and PMA.