Adenosine A1 receptor: Functional receptor-receptor interactions in the brain

Over the past decade, many lines of investigation have shown that receptor-mediated signaling exhibits greater diversity than previously appreciated. Signal diversity arises from numerous factors, which include the formation of receptor dimers and interplay between different receptors. Using adenosine A1 receptors as a paradigm of G protein-coupled receptors, this review focuses on how receptor-receptor interactions may contribute to regulation of the synaptic transmission within the central nervous system. The interactions with metabotropic dopamine, adenosine A2A, A3, neuropeptide Y, and purinergic P2Y1 receptors will be described in the first part. The second part deals with interactions between A1Rs and ionotropic receptors, especially GABAA, NMDA, and P2X receptors as well as ATP-sensitive K+ channels. Finally, the review will discuss new approaches towards treating neurological disorders

Neuroprotection by adenosine in the brain: From A1 receptor activation to A2A receptor blockade

Adenosine is a neuromodulator that operates via the most abundant inhibitory adenosine A1 receptors (A1Rs) and the less abundant, but widespread, facilitatory A2ARs. It is commonly assumed that A1Rs play a key role in neuroprotection since they decrease glutamate release and hyperpolarize neurons. In fact, A1R activation at the onset of neuronal injury attenuates brain damage, whereas its blockade exacerbates damage in adult animals. However, there is a down-regulation of central A1Rs in chronic noxious situations. In contrast, A2ARs are up-regulated in noxious brain conditions and their blockade confers robust brain neuroprotection in adult animals. The brain neuroprotective effect of A2AR antagonists is maintained in chronic noxious brain conditions without observable peripheral effects, thus justifying the interest of A2AR antagonists as novel protective agents in neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease, ischemic brain damage and epilepsy. The greater interest of A2AR blockade compared to A1R activation does not mean that A1R activation is irrelevant for a neuroprotective strategy. In fact, it is proposed that coupling A2AR antagonists with strategies aimed at bursting the levels of extracellular adenosine (by inhibiting adenosine kinase) to activate A1Rs might constitute the more robust brain neuroprotective strategy based on the adenosine neuromodulatory system. This strategy should be useful in adult animals and especially in the elderly (where brain pathologies are prevalent) but is not valid for fetus or newborns where the impact of adenosine receptors on brain damage is different

Evaluation of the Effect of Hydroalcoholic Extract of Citrullus colocynthis in Normoglycemic and Streptozocine (STZ) Induced Diabetic Male Rats

Introduction & Objective: Adverse side effects of chemical drugs for treatment of diabetes persuaded the using of medical plants. Citrullus colocynthis is a plant which has been used traditionally for treatment of diabetes. The purpose of this study was to evaluate the effect of hydroalcholic extract of Citrullus colocynthis fruit on normoglycemic and streptozocine induced diabetic rats. Materials & Methods: 45 male Wistar rats weighing, 250-350 gr, have been selected and randomly divided in seven groups. Group1 without any drugs usage, group 2 that received normal saline (IV) and distilled water (oral), group 3 received only streptozocine (IV), group 4 received only the extract of Citrullus colocynthis (1000 mg/kg), groups 5, 6 and 7 received 500, 1000 and 1500 mg/kg of Citrullus colocynthis extract after injection of STZ and induction of diabetes. Diabetes was induced by intravenous injection (45 mg/kg) of STZ. Blood sampling was provided directly from animal heart and blood sugar was measured. The collected data were analyzed by SPSS software using students t-test and ANOVA. Results: Mean of normal blood sugar in control group was 156.5±15.7 mg/dl which defined as normal blood sugar. Streptozocine significantly increased blood sugar (p<0.05). The Citrullus colocynthis extract with 500 mg/kg dosage has not significantly reduced the blood sugar but is dosage of 1000 and 1500 mg/kg significantly decreased the blood sugar in a dose-dependent mode (p<0.05). Results also showed that the extract in dosage of 1000 mg/kg did not have a significant effect on normoglycemic animals. Conclusion: Results of this study indicate that the extract of Citrullus colocynthis fruit dose-dependently reduced the blood glucose level in streptozocine-induced diabetic rats but did not have significant effect on normal blood sugar

Effects of Ascorbic Acid on the Amplitude of Ventral Tegmental Area Field Action Potential in Morphine-Exposed Rats (An Electrophysiology Study)

Introduction & Objective: Evidences have indicated that the Ventral Tegmental Area (VTA) is the major source of dopamine (DA) neurons projecting to cortical and limbic regions involved in cognitive and motivational aspects of addiction. Also, studies have indicated that the Ascorbic acid (vitamin C) can reduce the dependency symptoms of opioids such as morphine via effect of activity on dopaminergic neuron in VTA. For this reason, the aim of this study was to assess the effects of ascorbic acid on the amplitude of Ventral Tegmental Area field action potential in morphine-exposed rats. Materials & Methods: Forty male Wistar’s rats were used in this experimental study conducted at Yasuj University of Medical Sciences in 2010. Animals were randomly divided into four groups after electrode implantation and recovery period: 1. No- Vit C and No-Addicted group (nVitC.nA) 2. Vit C and No-Addicted group (VitC.nA) 3. No- Vit C and Addicted group (nVitCA) 4.Vit C and Addicted (VitC.A), The Vit C groups received 500 mg/kg of Vit C during 20 days. For addicted groups morphine was administrated once daily for 20 days. In the 20th day, the field potential recording was accomplished. Two-way ANOVA was used for data analysis followed by the Tukey test for post hoc analysis. Results were considered significant at P < 0.05. Results: This study shows the exposure to morphine declined the power of Delta and Beta bands (p<0.05) and Vit C solely enhance power of Theta and Beta (p<0.05, p<0.001) in VTA nuclei. Furthermore, Vit C could alter power of some bands which were affected by morphine. Therefore it seems that Vit C has an increasing effects on them (p<0.05). Conclusion: Although the effect of Vit C on power of the VTA bands is not well known, but it is supposed that this phenomenon can be related to alteration in activity of dopaminergic neuron in the brain