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Query: DrugBank:EXPT02427 (Atropine)
 3,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The possible involvement of cholinergic mechanisms and of GABA in the modulation and generation of ponto-geniculo-occipital (PGO) waves was studied using PGO waves induced by the benzoquinolizine derivative, Ro 4-1284 ( =PGO(1284)), and by p-chlorophenylalanine (=PGO(PCPA)), and continuously recorded and counted in the lateral geniculate bodies of unanaesthetized immobilized cats. Atropine had no significant effect on PGO(1284) but markedly depressed the density of PGO(PCPA) this effect of atropine was absent when the synthesis of noradrenaline (NA) was inhibited in addition to that of 5-hydroxytryptamine (5-HT). Arecoline and eserine at a low dose increased the density of PGO(PCPA). Both the stimulation of nicotinic receptors by nicotine and their blockade by mecamylamine reduced the amplitude of PGO(1284) and PGO(PCPA). Eserine, 0.3 mg kg(-1) i.v., had a similar effect. GABA injected into a lateral brain ventricle augmented the density of PGO(PCPA) but not the PGO(1284). Increasing the level of endogenous GABA by amino oxyacetic acid (AOAA) and by hydroxylamine affected PGO waves like GABA. Bicuculline tended to decrease the density of PGO(PCPA). Chlordiazepoxide increased the density of PGO(1284) and, more markedly, that of PGO(PCPA). The latter effect was prevented by atropine and by lesions placed in the amygdala, the septum and medial forebrain bundle several days prior to the acute experiment. It is concluded that synapse with nicotinic cholinergic receptors are prsent either in the neuronal network of the pontine reticular cells which trigger the PGO waves or within the pathway leading from this trigger area to the lateral geniculate body or within this structure. It is tentatively suggested that the noradrenergic neurones which depress the formaton of PGO waves, are under a modulating influence from limbic forebrain structures. The suggested pathway originating in the forebrain and projecting to the locus coeruleus seems to be inhibitory for the NA-neurones involved in the modulation of PGO waves and to contain muscarinic cholinergic and GABA-ergic synapse. Chlordiazepoxide might augment the density of PGO(PCPA) either by activating this pathway in the limbic forebrain or by enhancing GABA-ergic transmission at its ending.
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PMID:Drugs and PGO waves in the lateral geniculate body of the curarized cat. IV. The effects of acetylcholine, GABA and benzodiazepines on PGO wave activity. 104 75

Carnitine and acetylcarnitine have been demonstrated to be present in the CNS and to be involved in cholinergic mechanisms, even if their exact role in neurotransmission is still unknown. This microiontophoretic study was carried out on single cholinoceptive neurons of the somatosensory cortex in the rat in order to analyze the effects of L- and D-carnitine and L-acetylcarnitine on the spontaneous firing and the neuronal responses to some putative transmitters. L-carnitine and L-acetylcarnitine increased the spontaneous discharge rate, while D-carnitine was found to be ineffective. L-acetylcarnitine clearly potentiated the cholinergic excitatory responses. On the contrary, L-carnitine was found to reduce cholinergic responses in a great percentage of units and to inhibit L-acetylcarnitine-induced excitatory responses. Atropine blocked the increase in firing rate induced by L-carnitine and L-acetylcarnitine, thus suggesting for both of them a muscarinic activity. No interactions were observed between carnitines and GABA and glutamate. These results show that carnitine and acetylcarnitine are stereospecific neuroactive compounds with a cholinomimetic activity. They may play a role in a modulatory system for the cholinoceptive cortical neuron.
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PMID:Activity of L-carnitine and L-acetylcarnitine on cholinoceptive neocortical neurons of the rat in vivo. 168 39

The effects of 2-(p-chlorophenyl)-GABA (PCPGABA), thyrotropin releasing hormone (TRH), insulin and 2-deoxy-D-glucose (2DG) on gastric acid secretion, vagal nerve efferent activity and blood glucose level were examined in anesthetized rats. The latencies of onset of hypersecretion were 10 min for TRH (1 microgram/rat, i.c.), 20 min for PCPGABA (4 mg/kg, s.c.), 60 min for 2DG (200 mg/kg, i.v.) and 90 min for insulin (2 U/kg, i.v.), respectively. The secretagogue actions of PCPGABA and TRH were more potent than those of 2DG and insulin. All these secretagogues caused the efferent activation of the cervical vagal transmission, and the latencies for these vagal activation were shorter than those seen in gastric acid hypersecretion. Atropine and vagotomy completely abolished the secretagogue actions of these stimulants. PCPGABA and TRH were ineffective on the blood glucose level, unlike insulin and 2DG. These results suggest that PCPGABA, TRH, 2DG and insulin stimulate gastric acid secretion via central vagal cholinergic pathways, even though the precise mechanisms for each stimulant seem to be different.
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PMID:[Comparative effects of various centrally acting gastric secretagogues including PCPGABA and TRH in the perfused rat stomach preparation]. 217 Feb 51

Spontaneous EEG spikes (SPKs) were recorded from the CA1 region of the dorsal hippocampus in normal rats during behavioral states not accompanied by rhythmical slow activity (RSA) such as awake immobility and slow wave sleep. In the present study we examined the effects of various systemically administered drugs on hippocampal SPK activity. Three general anesthetics (ether, urethane and pentobarbital) all reduced SPK activity. At anesthetic doses both ether and pentobarbital completely abolished SPKs. This SPK abolition during anesthesia seemed qualitatively different from RSA-related SPK suppression in undrugged animals in that unlike the latter case RSA generation was not the cause of SPK abolition in the former case. Atropine (50-100 mg/kg, i.p.) did not change greatly SPK activity or its behavioral correlation. Diazepam (5-10 mg/kg, i.p.) increased amplitude and decreased frequency of hippocampal fast EEG activity, and reduced SPK activity. These effects may be based on the known action of diazepam to enhance GABA-mediated postsynaptic inhibition. At subepileptic doses (1-6 mg/kg, i.p.) the GABA antagonist bicuculline enhanced dramatically SPK-related activities. Particularly, SPK-concurrent population burst discharges in the pyramidal cell layer were greatly increased in amplitude and complexity after bicuculline. These results suggest that the SPK generation mechanism in the hippocampus is sensitive to the level of GABA-mediated inhibition.
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PMID:Spontaneous EEG spikes in the normal hippocampus. V. Effects of ether, urethane, pentobarbital, atropine, diazepam and bicuculline. 245 34

The effects of GABA, acetylcholine and carbachol on the spontaneous activity of afferent nerve fibers in the lateral line of Xenopus laevis are characterized. Atropine and bicuculline were also tested on drug- and water motion-evoked activity. GABA (0.019-1.25 mM) suppressed and both acetylcholine (1.25-80 microM) and carbachol (1.25-40 microM) increased spontaneous activity. These actions were blocked by bicuculline (100 microM) and atropine (4 microM) respectively. Atropine (20 microM) and bicuculline (100 microM) had no effect on water motion-evoked activity. The results characterize actions of GABA and acetylcholine not previously described and provide evidence that does not support the hypothesis that GABA or acetylcholine are the afferent transmitter.
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PMID:Comparative actions of GABA and acetylcholine on the Xenopus laevis lateral line. 286 Oct 15

Field stimulation produced reproducible contractions of the mouse isolated urinary bladder whose amplitude was frequency-related. These contractions were partially sensitive to atropine (3 microM), unaffected by hexamethonium (10 microM) and almost abolished by tetrodotoxin (0.5 microM). Atropine (3 microM) suppressed contractions produced by exogenous acetylcholine thereby indicating atropine-resistance of the nerve-mediated contractions. Nerve-mediated contractions of the mouse urinary bladder were enhanced by physostigmine (0.1-0.5 microM) and inhibited by hemicholinium-3 (0.5 mM) thus confirming the presence of a cholinergic component in the excitatory postganglionic innervation. Atropine (3 microM) inhibition of the nerve-mediated contractions increased with increasing duration and strength of the train of stimulation. The nerve-mediated contractions of the mouse bladder were unaffected by phentolamine (0.2 microM), propranolol (0.3 microM) or indomethacin (5 microM). ATP (1mM) the major candidate for the role of nonadrenergic-noncholinegic (NANC) excitatory neurotransmitter in the mammalian urinary bladder produced a contraction of the mouse isolated bladder. Exposure to the stable ATP analogue alpha, beta-methylene ATP (APCPP) or beta, gamma-methylene ATP (APPCP) produced a partial desensitization of the nerve-mediated response which, for APCPP, was greater in the presence than in the absence of atropine (3 microM). In the presence of atropine (3 microM) and after APCPP desensitization the amplitude of the response to field stimulation amounted to about 20% of the original response and was sensitive to tetrodotoxin, indicating that it is nerve-mediated. GABA (0.001-0.3 mM) inhibited the amplitude of field stimulation induced contractions of mouse urinary bladder. This effect was mimicked by the selective GABAB receptor agonist, (+/-)-baclofen, but not by the selective GABAA receptor agonist, homotaurine. GABA and (+/-)-baclofen exhibited cross-desensitization. The GABA-or (+/-)-baclofen-induced inhibition of the nerve-mediated contractions were reduced by previous exposure to homotaurine (1 mM) or to 5-aminovaleric acid (2 mM), two GABAB receptor antagonists. On the other hand the inhibitory effects of GABA or (+/-)-baclofen were unaffected by picrotoxin (0.1 mM), a selective GABAA receptor antagonist. The inhibitory effect of GABA on nerve-mediated contractions was reduced in the presence of atropine or hemicholinium-3 as well as following desensitization of P2-purinoreceptors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The postganglionic excitatory innervation of the mouse urinary bladder and its modulation by prejunctional GABAB receptors. 300 24

This study investigated the functional capacity of intrastriatal grafts of embryonic striatal tissue in rats with unilateral ibotenic acid lesions of the neostriatum. The group of grafted rats was compared with lesion-alone and control groups for motor bias, as assessed by tests of rotation induced by dopaminergic, cholinergic and GABAergic drugs, and of skilled paw reaching. Unilateral striatal lesions induced marked ipsilateral turning to apomorphine and methamphetamine, which was substantially ameliorated in the grafted rats. Atropine induced similar rates of moderate (but non-significant) ipsilateral turning in the lesion and graft groups, whereas muscimol and gamma-acetylenic GABA induced no turning bias in any group. The lesioned rats showed a strong bias in their preference to use the paw ipsilateral to the lesion when reaching for food pellets, and a decline in reaching success with both paws. The grafts did not influence the ipsilateral paw preference in this task, but did provide a substantial improvement in the animal's reaching accuracy and ability to retrieve food with either paw. The results indicate that striatal grafts can provide a substantial amelioration of motor impairments induced by striatal lesions. Moreover they suggest that the graft's influence on the host brain is itself under the functional regulation of an afferent dopaminergic input from the host brain.
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PMID:Striatal grafts in rats with unilateral neostriatal lesions--III. Recovery from dopamine-dependent motor asymmetry and deficits in skilled paw reaching. 338 Mar 1

Baclofen [beta-(p-chlorophenyl)-gamma-aminobutyric acid], a lipophilic derivative of GABA, was studied for its effect upon the efferent activity of the left cervical vagus in urethane-anesthetized rats. Baclofen (4 mg/kg, s.c.) produces neural discharges in the multifiber vagus preparation. The time course of vagal activation is well correlated with the profile of stimulation of gastric acid secretion recorded every 2 min. Atropine pretreatment (1 mg/kg) did not modify baclofen stimulation of vagal activity. These results demonstrated that a GABAB receptor agonist stimulates the parasympathetic outflow through mechanisms independent of interaction with muscarinic receptors leading to stimulation of gastric acid secretion.
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PMID:Gastric acid and vagus nerve response to GABA agonist baclofen. 401 Apr 64

1. In cats anaesthetized with pentobarbitone sodium the effect on arterial blood pressure was examined of substances applied bilaterally to the exposed ventral surface of the brain stem by means of Perspex rings placed lateral to the pyramids and caudal to the trapezoid bodies. Routinely, atropine methyl nitrate, which does not pass the blood-brain barrier, was injected I.V.2. The cholinomimetic substances carbachol and physostigmine, and the amino acids glycine and GABA, caused a fall in arterial blood pressure.3. Atropine produced a small but definite rise in arterial blood pressure, antagonized the depressor effects of the cholinomimetic substances, but not those of the amino acids.4. Strychnine, leptazol and tubocurarine, caused a rise in arterial blood pressure.5. The depressor and pressor effects are due to changes in vasomotor tone. They are central effects brought about by penetration of the substances into the brain tissue from the ventral surface of the brain stem. They are not due to their absorption into the blood stream.6. The depressor effects of the cholinomimetic substances may imitate the action of cholinergic neurones, and those of the amino acids that of central inhibitory neurones ending on cells near the ventral surface of the brain stem and exerting an inhibitory influence on vasomotor tone. The pressor effects of strychnine and tubocurarine may in part result from ;disinhibition', i.e. from an antagonistic action produced by these drugs on the amino acids released from the central inhibitory neurones.
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PMID:Blood pressure effects obtained by drugs applied to the ventral surface of the brain stem. 472 30

The effects of GABA and selective GABAA and GABAB receptor agonists and antagonists have been investigated on field stimulation-induced contractions (0.1 Hz) of rabbit urinary bladder strips in-vitro. Atropine inhibits twitches of bladder strips obtained from the bladder dome more effectively than those obtained from the bladder base. Both GABA and the selective GABAB receptor agonist, (+/-)-baclofen inhibited field stimulation-induced contractions to about the same extent, while the selective GABAA receptor agonist, homotaurine had no effect. In the presence of atropine, GABA failed to inhibit further the amplitude of twitches. The effects of either GABA or (+/-)-baclofen were antagonized by the GABAB receptor antagonists homotaurine and 5-aminovaleric acid, while the GABAA receptor antagonist picrotoxin had no effect. Neither GABA nor (+/-)-baclofen had any significant effect on acetylcholine-induced contractions of unstimulated bladder strips, but they were abolished by atropine. These results suggest that GABAB receptors inhibit field stimulation-induced contractions of rabbit bladder muscle by reducing the amount of acetylcholine released per nerve impulse.
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PMID:GABAB receptor mediated inhibition of field stimulation-induced contractions of rabbit bladder muscle in-vitro. 614 68


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