Receptors malfunction

While there are some reports of increased NMDA and non-NMDA receptor number in various cortical regions of schizophrenics including the prefrontal cortex, there are also indications of impaired glutamate innervation, such as reduction in its neuronal uptake sites (Ishimaru, Kurumaji and Torn 1994). Also it has been found that levels of the mRNA for the NRI subunit of the NMDA receptor in the hippocampus and its D-aspartate binding sites in the temporal cortex are both reduced more on the left than right side in schizophrenic brain. This is another indication of greater malfunction on the left side of the brain and the possibility that some schizophrenic symptoms arise from an imbalance between cross-cortical activity. 

The undisputed efficacy of benzodiazepines in relief of anxiety led to the question of whether this disorder could arise from abnormal concentrations in the brain of an endogenous ligand or a malfunction of the benzodiazepine/GABA receptor system. An important study, aimed at distinguishing between these possibilities, has been carried out in humans (Nutt et al. 1990) and was based on the premise that anxiety could be caused by either ... 

Apomorphine is an agonist at both the and D2 receptors. From the pathological viewpoint, a malfunction of the receptors has been implicated in the negative s)nnptoms of schizophrenia but as there is a close interaction between these receptor types it is difficult to conclude whether the changes seen in schizophrenia are attributable to a primary decrease in receptor function or an increase in D2 receptor function. The function of the D5 receptors is unclear these receptors, though widely distributed in the brain, are only present in a relatively low density in comparison to the other dopamine receptor types. 

The D2 receptor types, besides being subdivided into D3 and D4 types, are further divided into the D2 long and D2 short forms. D2 antagonists, in addition to virtually all therapeutically active neuroleptics, also include such novel drugs as raclopride, eticlopride and sniperone while quinpirole is an example of a specific D2 receptor agonist. The latter drugs are not available for therapeutic use. A malfunction of the D2 receptors has been associated with psychosis, extrap)n amidal side effects and hyperprolactinaemia. 

The central cholinergic system has been implicated in the pathogenesis of affective disorder and in memory function, which is frequently found to be malfunctioning in depressed patients. The memory deficit elicited by chronic ECT in both patients and animals may be related to the decreased density and function of central muscarinic receptors, but it should be emphasized that the changes reported in cholinergic function are small and their relevance to the clinical situation remains to be established. 

Vitamin A deficiency can result from insufficient dietary intake, from malabsorption and it has been recognized that also malfunction of RAR-receptors can lead to symptoms of vitamin A deficiency. These symptoms include skin lesions, night blindness, corneal ulcerations and conjunctivitis and poor bone remodeling. Vitamin A deficiency associated with malnutrition is wide spread in large parts of the world and may be fatal in infants and young children suffering from kwashiorkor or marasmus. 

Bi2 are only about 2 meg, it would take about 5 years for all of the stored vitamin B12 to be exhausted and for megaloblastic anemia to develop if Bi2 absorption were stopped. Vitamin B12 in physiologic amounts is absorbed only after it complexes with intrinsic factor, a glycoprotein secreted by the parietal cells of the gastric mucosa. Intrinsic factor combines with the vitamin Bi2 that is liberated from dietary sources in the stomach and duodenum, and the intrinsic factor-vitamin Bi2 complex is subsequently absorbed in the distal ileum by a highly selective receptor-mediated transport system. Vitamin Bi2 deficiency in humans most often results from malabsorption of vitamin B12 due either to lack of intrinsic factor or to loss or malfunction of the specific absorptive mechanism in the distal ileum. Nutritional deficiency is rare but may be seen in strict vegetarians after many years without meat, eggs, or dairy products. 

Receptors are theoretical sites of malfunctioning which could lead to nervous or mental disorders. True or False. 

It should be pointed out that all these effects on response kinetics of the EAG could be caused by malfunction in a subset of ORNs rather than represent changes in kinetics of the receptor potentials. Since EAG and EPG represent summations of such potentials, and ORNs differ greatly in their temporal response dynamics, a deletion of a subset of ORNs with a minor contribution to final amplitude could change the steepness of rise or fall of the EAG. 

Mental disorders, also called affective disorders, are multi-level, multi-scale and multiple-system diseases (Fig. 7.1). Mental disturbances generally go along with disturbances of autonomous functions. These essentially are (1) sleep disturbances, both sleep duration and sleep pattern, and (2) disturbances of the hypothalamic-pituitary-adrenal (HPA) axis, the so-called stress axis with elevated cortisol levels. It can be expected that disturbances of autonomous control systems as well as mood are caused by neuronal malfunctioning which may concern practically all neuronal levels systemic interactions, neuronal network connections, single neuron dynamics, synaptic transmitters and/or receptors, ion channels, second messengers, and gene expression (Fig. 7.1a). Nevertheless, despite a manifold of data, there are only vague ideas so far about the differences in neuronal dynamics in the brain of a chronically depressed person compared with a person with a sensitive but balanced mood. 

Some time ago, one of us suggested that insulin might exert its actions through a multipathway mechanism , whereby the membrane-bound receptor generated a number of distinct signals [87]. There appears to be an increasing body of evidence consistent with this proposal (Fig. 5). Certainly it would offer an explanation for the. plethora of actions of insulin and diversity of (selective) insulin-resistant conditions, where malfunction of one or more of these pathways occurs. 

In its most elemental definition, a disease occurs when something in the body malfunctions. Heart attack The walls of a coronary artery become too clogged with fatty deposits, blocking the flow of blood to the heart. Cancer A mutated cell replicates out of control. Infection A virus overcomes the body s immune system. To get the body back to normal, scientists try to find a molecule that will intercept the malfunction. If the disease is caused by the behavior of an enzyme, the molecule could block the enzyme, modify its behavior, or block the receptor it attaches to. In pharmaceutical talk, that magic molecule has been known as a compound. To the public, it s a drug. 

All related disorders are attributed to a malfunction of the basal ganglia (which contain a rich array of neurotransmitters and receptors controlling muscular movements) and of the substantia nigra (where dopamine is produced). Dopamine is one of the brain chemicals involved in the control of physical movement, and Parkinsonism is characterized by dopamine depletion. Secondary Parkinsonism, in which symptoms are of a passing nature, is due to temporary dopamine depletion, induced most commonly by antipsychotic drugs. 

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