Altered cholinergic metabolism and muscarinic receptor linked second messenger pathways after chronic exposure to dichlorvos in rat brain

2007 ◽  
Vol 23 (1) ◽  
pp. 25-37 ◽  
Author(s):  
Geetu Raheja ◽  
Kiran Dip Gill
Keyword(s):  
Brain Stem ◽  
Muscarinic Receptor ◽  
Body Weight Gain ◽  
Second Messenger ◽  
Brain Regions ◽  
Choline Uptake ◽  
Maximal Effect ◽  
Male Wistar Rats ◽  
Messenger System ◽  
Second Messenger Pathways

Chronic dichlorvos exposure (6mg/kg b.wt/day) for a period of 8 weeks resulted in significant reduction in body weight gain of the male Wistar rats. However, the dietary intake remained unchanged in experimental animals following dichlorvos treatment. Activity of the synthesizing enzyme of acetylcholine (ACh) ie, choline acetyltransferase, was found to be significantly increased and the activity of hydrolyzing enzyme, acetyl cholinesterase (AChE), was inhibited in all the three brain regions studied. Chronic dichlorvos treatment also caused significant reduction in both high affinity (HA) and low affinity (LA) choline uptake (CU), with maximal effect being observed in the brain stem followed by cerebellum and cerebrum. Muscarinic receptor binding was significantly decreased in brain stem and cerebellum as reflected in the decreased receptor number (Bmax), without any change in the binding affinity (Kd) of the receptors. Dichlorvos treatment caused marked inhibition in cAMP synthesis as indicated by decreased adenylate cyclase activity as well as cAMP levels in cerebrum, cerebellum and brain stem. Our study shows that organophosphates may interact with muscarinic receptor-linked second messenger system and this could be a potential mechanism for the neurotoxic effects observed after repeated exposure to low levels of organophosphates, which are unexplainable on the basis of cholinergic hyperactivity. Toxicology and Industrial Health 2007; 23: 25—37.

scholarly journals Long-term atropine treatment lowers the efficacy of carbachol to stimulate phosphatidylinositol breakdown in the cerebral cortex and hippocampus of rats

1988 ◽  
Vol 250 (3) ◽  
pp. 727-734 ◽  
Author(s):  
L Goobar ◽  
T Bartfai
Keyword(s):  
Cerebral Cortex ◽  
Muscarinic Receptor ◽  
Inositol Phosphates ◽  
Hippocampal Slices ◽  
Qualitative Change ◽  
Brain Regions ◽  
Maximal Effect ◽  
Long Term Treatment ◽  
Atropine Treatment

The effect of long-term treatment with atropine, a muscarinic antagonist, known to cause up-regulation of receptor numbers, was examined on the muscarinic-receptor-mediated stimulation of phosphoinositide breakdown in the rat cerebral cortex and hippocampus. Although the numbers of both M1 muscarinic receptors, as measured by [3H]pirenzepine binding, and M1 and M2 receptors increased in both brain regions, the maximal breakdown of myo-[3H]inositol-labelled phosphoinositides was unaltered in the presence of carbachol at a saturating concentration (10(-2) M). In fact the efficacy of carbachol was decreased in slices from atropine-treated cerebral cortex [EC50 (concentration producing half-maximal effect) = 93 microM] as compared with the saline-treated control (EC50 = 23 microM)(P less than 0.005). Similarly the EC50 value (23 microM) in hippocampal slices from saline-treated rats increased in atropine-treated rats to 126 microM (P less than 0.005). This lowered efficacy of muscarinic stimulation could not be explained in terms of residual atropine in the tissue from treated rats. The noradrenaline- or serotonin (5-hydroxytryptamine)-stimulated breakdown or the K+ potentiation of the muscarinic-receptor-stimulated breakdown of [3H]phosphoinositides was not affected by the atropine treatment. Chromatography of the released [3H]inositol phosphates shows that atropine treatment did not cause any qualitative change in the pattern of [3H]inositol phosphates released by carbachol stimulation.

Comparative Efficacies of Antimigraine Drugs Using Nitroglycerin Induced Migraine Rats Model

2021 ◽  
pp. 34-42
Author(s):  
Anson S. Maroky ◽  
V. Parthasarathy
Keyword(s):  
Social Interaction ◽  
Brain Stem ◽  
Brain Regions ◽  
Behavioural Activity ◽  
Antimigraine Drugs ◽  
Calcitonin Gene ◽  
Male Wistar Rats ◽  
Interaction Task ◽  
Nonpharmacological Intervention ◽  
Anxiety Depression

Aim: The migraine pathology is still not explained effectively. There is a common relationship between anxiety, depression, and migraine. So the aim of the study to illustrate effectively the behavioural and biomarker changes in the migraine condition. Methods: Nitroglycerin (NTG) induced migraine rats model was used the present study. Twenty-five male Wistar rats were randomly divided into five groups. Ergotamine, sumatriptan, and BIBN4096 were used as antimigraine drugs. The behavioural activity was measured by scratching head, body shaking, and social interaction task. ELISA detected biomarkers like interleukin 6 (IL-6),                  Substance P (SP) and 5-hydroxytryptamine (5-HT) in various rats brain regions such as cortex, brain stem, trigeminal ganglion. Results: A significant reduction in hyperalgesic response and behavioral changes like scratching head, body shaking and social interaction task. Biomarkers like 5-HT, SP and IL-6 were significantly reduced in the various brain regions such as prefrontal cortex, brain stem and trigeminal ganglia of the rats in the BIBN4096 treated groups. Conclusion: The present study showed a good antimigraine efficacy with a calcitonin gene-related peptide (CGRP) antagonistic agent BIBN4096 than ergotamine and sumatriptan but still lack of behavioural pattern, need to explore nonpharmacological intervention along with the drug treatment.

170: Do Alpha1Adrenoceptors in pig Urethra Demonstrate agonist-Specific Coupling to Distinct Second Messenger Pathways ?

2005 ◽  
Vol 173 (4S) ◽  
pp. 46-46
Author(s):  
Rachael L. Scott ◽  
Christopher Chappie ◽  
Russell Chess-Williams
Keyword(s):  
Second Messenger ◽  
Second Messenger Pathways

scholarly journals MCI-225 enhances noradrenergic function by modulating second messenger system in the rat brain

1995 ◽  
Vol 67 ◽  
pp. 146
Author(s):  
Takavuki Yuasa ◽  
Junichi Eguchi ◽  
Mitsuo Eeawa ◽  
Ken-Ichi Saito
Keyword(s):  
Rat Brain ◽  
Second Messenger ◽  
Messenger System ◽  
Noradrenergic Function

scholarly journals Emotional Reactions to Music in Dementia Patients and Healthy Controls: Differential Responding Depends on the Mechanism

2021 ◽  
Vol 4 ◽  
pp. 205920432110101
Author(s):  
Gonçalo T. Barradas ◽  
Patrik N. Juslin ◽  
Sergi Bermúdez i Badia
Keyword(s):  
Episodic Memory ◽  
Brain Stem ◽  
Geriatric Depression Scale ◽  
Depression Scale ◽  
Basic Research ◽  
Brain Regions ◽  
Emotional Reactions ◽  
Dementia Patients ◽  
Significant Difference ◽  
Brain Stem Reflex

Music is frequently regarded as a unique way to connect with dementia patients. Yet little is known about how persons with dementia respond emotionally to music. Are their responses different from those of healthy listeners? If so, why? The present study makes a first attempt to tackle these issues in a Portuguese context, with a focus on psychological mechanisms. In Experiment 1, featuring 20 young and healthy adults, we found that musical excerpts which have previously been shown to activate specific emotion induction mechanisms (brain stem reflex, contagion, episodic memory, musical expectancy) in Sweden were valid and yielded predicted emotions also in Portugal, as indexed by self-reported feelings, psychophysiology, and post hoc mechanism indices. In Experiment 2, we used the same stimuli to compare the responses of 20 elderly listeners diagnosed with Alzheimer’s disease (AD) with those of 20 healthy listeners. We controlled for cognitive functioning (Mini-Mental State Examination) and depression (Geriatric Depression Scale). Our predictions about how mechanisms would be differentially affected by decline in brain regions associated with AD received support in that AD patients reported significantly lower levels of (a) sadness in the contagion condition, (b) happiness and nostalgia in the episodic memory condition, and (c) anxiety in the musical expectancy condition. By contrast, no significant difference in reported surprise was found in the brain stem reflex condition. Implications for musical interventions aimed at dementia are discussed, highlighting the key role that basic research may play in developing applications.

scholarly journals A Blunted Sympathetic Function and an Enhanced Nitrergic Activity Contribute to Reduce Mesenteric Resistance in Hyperthyroidism

2021 ◽  
Vol 22 (2) ◽  
pp. 570
Author(s):  
Laia Cros-Brunsó ◽  
Laura Camacho-Rodríguez ◽  
Ángel Martínez-González ◽  
Pablo Llévenes ◽  
Mercedes Salaices ◽  
...  
Keyword(s):  
Citrate Synthase ◽  
Purinergic Receptor ◽  
Body Weight Gain ◽  
Electrical Field Stimulation ◽  
Alpha Adrenoceptor ◽  
Adrenoceptor Antagonist ◽  
Sympathetic Function ◽  
Vasoconstrictor Response ◽  
Relevant Role ◽  
Male Wistar Rats

We aimed to determine whether an experimental model of hyperthyroidism could alter the function of sympathetic and nitrergic components of mesenteric innervation. For this purpose, male Wistar rats were divided into (1) control rats (CT) and (2) rats infused with L-Thyroxine (HT). Body weight gain and adipose tissue accumulation were lower in HT rats, while systolic blood pressure and citrate synthase activity in the soleus muscle were increased by HT. In segments from the superior mesenteric artery, the application of an electrical field stimulation (EFS) induced a vasoconstrictor response, which was lower in arteries from HT animals. The alpha-adrenoceptor antagonist phentolamine diminished EFS-induced vasoconstriction to a lower extent in HT arteries, while the purinergic receptor antagonist suramin reduced contractile response to EFS only in segments from CT. In line with this, noradrenaline release, tyrosine hydroxylase expression and activation and dopamine β hydroxylase expression were diminished in HT. The unspecific nitric oxide synthase (NOS) inhibitor L-NAME increased EFS-induced vasoconstriction more markedly in segments from HT rats. NO release was enhanced in HT, probably due to an enhancement in neuronal NOS activity, in which a hyperactivation of both PKC and PI3K-AKT signaling pathways might play a relevant role. In conclusion, perivascular mesenteric innervation might contribute to reduce the vascular resistance observed in hyperthyroidism.

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