Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropeptides: corticotropin releasing factor (CRF), neuropeptide Y (NPY) and somatostatin (STS) have been associated with depression and anxiety, while neurotensin (NT), calcitonin gene-related peptide (CGRP) and tachykinins [neurokinin A (NKA) and substance P (SP)] are presumed to also play a role in the function of the dopaminergic system. Moreover, investigations in the past decade have shown that psychotomimetics and antipsychotic drugs as well as lithium affect brain synthesis, tissue concentrations, and release of some neuropeptides. In view of the above, experiments were carried out to explore whether changes in neuropeptides constitute one of the mechanisms of action of electroconvulsive treatment (ECT). Human cerebrospinal fluid (CSF) was studied before and after ECT, and brains from healthy and models of depression rats were investigated in electroconvulsive stimuli (ECS)-treated and sham-treated animals. The major findings were that a series of ECTs, in parallel to clinical recovery, increased CSF concentrations of NPY-like immunoreactivity (-LI), STS-LI, and CRF-LI, and in one study endothelin-LI. A series of ECS, but not a single treatment, reproducibly elevated concentrations of NPY-LI, NKA-LI, and STS-LI--but not NT-LI, SP-LI, galanin-LI, or CGRP-LI--in hippocampus, frontal cortex, and occipital cortex. No changes were measured in other regions, e.g., striatum. NPY and STS mRNAs were also increased indicating that ECS affects peptide synthesis. Generalized seizures induced by, e.g., kainic acid or pentylenetetrazole, had similar effects on neuropeptides. The changes persisted for at least 1 week after the last treatment. Pretreatment with compounds reducing seizures, such as benzodiazepines and MK-801; had no effect on magnitude of neuropeptide changes although the seizure duration was decreased by > 50%. On the basis of these findings, it is suggested that neuropeptides are involved in ECT's mechanisms of action. Since ECT is therapeutically efficient in both schizophrenia and depression and, taking into account that antipsychotic drugs and psychotomimetics as well as lithium selectively affect some neuropeptides, it is hypothesized that distinct combinations of neuropeptide and monoamine changes in selected neuronal populations constitute the underpinnings of ECT's effects on specific disease symptoms, conceivably independent of diagnosis.
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PMID:Neuropeptides and electroconvulsive treatment. 1018 19

This review provides an overview of preclinical and clinical evidence of a role for the neuroactive peptides cholecystokinin (CCK), corticotropin-releasing factor (CRF), neuropeptide Y (NPY), tachykinins (i.e., substance P, neurokinin [NK] A and B), and natriuretic peptides in anxiety and/or stress-related disorders. Results obtained with CCK receptor antagonists in animal studies have been highly variable, and clinical trials with several of these compounds in anxiety disorders have been unsuccessful so far. However, future investigations using CCK receptor antagonists with better pharmacokinetic characteristics and animal models other than those validated with the classical anxiolytics benzodiazepines may permit a more precise evaluation of the potential of these compounds as anti-anxiety agents. Results obtained with peptide CRF receptor antagonists in animal models of anxiety convincingly demonstrated that the blockade of central CRF receptors may yield anxiolytic-like activity. However, the discovery of nonpeptide and more lipophilic CRF receptor antagonists is essential for the development of these agents as anxiolytics. Similarly, there is clear preclinical evidence that the central infusion of NPY and NPY fragments selective for the Y1 receptor display anxiolytic-like effects in a variety of tests. However, synthetic nonpeptide NPY receptor agonists are still lacking, thereby hampering the development of NPY anxiolytics. Unlike selective NK1 receptor antagonists, which have variable effects in anxiety models, peripheral administration of selective NK2 receptor antagonists and central infusion of natriuretic peptides produce clear anxiolytic-like activity. Taken as a whole, these findings suggest that compounds targeting specific neuropeptide receptors may become an alternative to benzodiazepines for the treatment of anxiety disorders.
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PMID:Is there a future for neuropeptide receptor ligands in the treatment of anxiety disorders? 1034 56

The viral transneuronal labeling method was used to localize sympathetic-related neurons in the preoptic region following pseudorabies virus (PRV) injections into either the superior cervical ganglion, stellate ganglion, celiac ganglion, or adrenal gland of rats. A general pattern of infection was detected. First, neuronal labeling was found in the medial preoptic area, medial preoptic nucleus, median preoptic nucleus, and lateral preoptic area, and then it spread to the anteroventral periventricular, anteroventral preoptic, and parastrial nuclei. Finally, the forebrain circumventricular organs: organum vasculosum of the lamina terminalis (OVLT) and subfornical organ (SFO) became infected. Neuropeptide-containing preoptic neurons were analyzed following PRV injections in the stellate ganglion. Some thyrotropin-releasing hormone and neurotensin neurons were labeled, but none of the calcitonin gene-related peptide, cholecystokinin, corticotropin-releasing factor, galanin, luteinizing hormone-releasing hormone, enkephalin, substance P, or tyrosine hydroxylase neurons were PRV infected. Two major sympathetic networks appear to be represented in the preoptic region. One is linked to the OVLT, SFO, and anteroventral third ventricular (AV3V) region, sites previously implicated in fluid and electrolyte balance as well as cardiovascular control. The other descending sympathetic pathway appears to target the medial preoptic nucleus as its key nodal point, receiving inputs from infralimbic cortex and limbic regions, such as the lateral septum, medial nucleus of the amygdala, subiculum, and amygdalohippocampal area, and then, projecting caudally to the hypothalamus and brainstem. This second sympathetic network may subserve affiliative, defensive and sexual behaviors.
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PMID:Sympathetic-related neurons in the preoptic region of the rat identified by viral transneuronal labeling. 1051 2

Prolonged emotional stress is an important factor in the development of neurogenic hypertension, but its mechanism is still unclear. The purpose of the present study is to analyze the possible neural basis of hypertension induced by prolonged emotional stress. In the brain many nuclei are involved in emotional reaction, stress or defense response; among them the nucleus amygdaloideus centralis (AC) is the most important one which widely connects with other nuclei controlling emotion and stress, such as nucleus ventromedialis (NVM), nucleus dorsomedialis (NDM), nucleus paraventricularis (NPV) etc. These nuclei contain corticotropin releasing factor (CRF)- and substance P (SP)-immunoreactive cell bodies, nerve terminals and corresponding receptors. Our previous and present studies showed that microinjection of CRF or SP into these nuclei induced pressor responses. These data imply that excitation of the AC can activate many nuclei controlling emotion and stress via CRF and SP, and excessive activities of these nuclei may be the neural basis of hypertension induced by prolonged emotional stress. The present study revealed that (1) the AC pressor response to glutamate (Glu) could be reduced by preinjection of CRF antagonist (alpha-Helical CRF[9-41] or SP antagonist ([D-Pro(2), D-Phe(7), D-Trp(9)]-substance P) into bilateral NVM, (2) the NVM pressor response to Glu were decreased by pretreatment of the NDM with CRF- or SP-antagonist, (3) the AC-, NVM- or NDM-pressor responses were all attenuated by preinjection of CRF- or SP-antagonist into bilateral NPV or rostral ventrolateral medulla (RVL). The results indicate that excitation of the AC can indirectly activate the NPV and RVL to evoke pressor response via the NVM-NDM, CRF and SP are transmitters in each connection of this pathway; this is one component of the mechanism underlying the AC pressor response. Taken together with the findings of our previous studies, it provides neurophysiological basis for the above-mentioned implications.
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PMID:Corticotropin releasing factor and substance P mediate the nucleus amygdaloideus centralis-nucleus ventromedialis-nucleus dorsomedialis pressor system. 1052 35

Many neuropeptides are involved in the control of sexual behaviour at the central level. Among these, the most studied are adrenocorticotropin, alpha-melanocyte stimulating hormone, oxytocin and opioid peptides. This attempt to review old and new neuropharmacological, biochemical and psychobiological studies in this field, shows that all these neuropeptides apparently facilitate sexual behaviour, except for opioid peptides, which inhibit sexual performance, in most of the species studied so far (rats, mice, monkeys and humans). However, gonadotropin-releasing hormone, corticotropin releasing factor, neuropeptide Y, galanin, cholecystokinin, substance P and vasoactive intestinal peptide may be also involved in the control of sexual behaviour. Apparently, corticotropin releasing factor, neuropeptide Y and cholecystokinin inhibit, while substance P and vasoactive intestinal peptide facilitate, sexual behaviour. In contrast, gonadotropin-releasing hormone has been reported to exert a facilitative, inhibitory or no effect at all on sexual behaviour. Galanin was also shown either to facilitate or inhibit sexual behaviour. The above-mentioned putative role of the neuropeptides in sexual behaviour derives mainly from studies done in rats. In these studies, neuropeptides, their antisera or drugs that act as agonists or antagonists of neuropeptide receptors, were tested for their effect on sexual behaviour after systemic, intracerebroventricular, or intracerebral administration. The latter were infused into brain areas relevant for sexual behaviour, such as the medial preoptic area, and the ventromedial and paraventricular nuclei of the hypothalamus. The above studies show that little information is available on the mechanisms by which neuropeptides influence sexual behaviour. Also unclear is whether the above neuropeptides influence the anticipatory phase (sexual arousal and/or motivation) or the consummatory phase (performance) of sexual behaviour, except for opioid peptides. New information about the role of neuropeptides may come from the application of molecular biology and genetic manipulation techniques to the study of sexual behaviour. Of these, FOS protein determination, antisense oligonucleotides aimed at the neutralisation of neuropeptide and/or neuropeptide receptor mRNAs in specific brain areas, and gene ablation seem the most promising. Although still in the early stages, it is likely that these methodologies will provide new insights into the role of neuropeptides in the control of sexual behaviour.
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PMID:Neuropeptides and sexual behaviour. 1064 21

This review considers future directions for developing effective drugs for posttraumatic stress disorder (PTSD). At present, we have embarked upon an empirical approach in which pharmacologic research consists of clinical trials with agents, such as antidepressants, anxiolytics, and anticonvulsants, initially developed for different purposes. The approach taken here is theoretical rather than empirical, starting with what is known about the unique pathophysiology of PTSD and then predicting the types of pharmacologic agents that might prove effective in the future. Such classes of compounds include corticotropin-releasing factor antagonists, neuropeptide Y enhancers, antiadrenergic compounds, drugs to down-regulate glucocorticoid receptors, more specific serotonergic agents, agents normalizing opioid function, substance P antagonists, N-methyl-D-aspartate facilitators, and antikindling/antisensitization anticonvulsants.
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PMID:What might the psychobiology of posttraumatic stress disorder teach us about future approaches to pharmacotherapy? 1079 9

Cyclic vomiting syndrome (CVS) remains a mysterious disorder despite our increasing knowledge since its classic description by Gee in 1882. Its hallmark feature of recurrent, explosive bouts of vomiting punctuating periods of normal health causes substantial medical morbidity (50% of patients require intravenous therapy), as well as significant time lost from school (20 school absences per year) and work. Limited epidemiologic data indicate that CVS may occur more commonly than previously thought, affecting as many as 1.9% of school-aged children. Besides the relentless vomiting, the child usually has pallor (87%), lethargy (91%), anorexia (74%), nausea (72%), and abdominal pain (80%). There is evidence of clinical and physiologic overlap among CVS, abdominal migraine, and migraine headaches. We propose revised criteria for abdominal migraine that include pain as the predominant and consistent symptom, lack of abnormal screening tests, and in retrospect, either subsequent development of migraines or positive response to antimigraine medication. Besides migraines, other etiologic possibilities include mitochondrial DNA mutations, ion channelopathies, excessive hypothalamic-pituitary-adrenal axis activation, and heightened autonomic reactivity. The differential diagnosis includes idiopathic CVS (88%); gastrointestinal disorders (7%), including serious surgical disorders (e.g., malrotation); and extraintestinal disorders (5%), including serious surgical (brain stem neoplasm) and metabolic disorders (e.g., fatty acid oxidation disorder). Within the idiopathic group, there may be migraine, Sato's neuroendocrine, mitochondrial, and other subgroups. Treatment includes avoidance of triggers, prophylactic medication, supportive care, abortive medication, and family support. In the future, investigation into mitochondrial DNA mutations, ion channel defects, corticotropin-releasing factor, and serotonin and tachykinin receptor physiology and pharmacology may help discover the etiology and pathogenesis of this disorder.
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PMID:Cyclic vomiting syndrome: evolution in our understanding of a brain-gut disorder. 1095 42

The stress response in a healthy organism is generally viewed as a warning and thus a protective reaction to a threat. However, the response may be deleterious if it is linked to an inflammatory stimulus or if it proceeds an inflammatory event. Prior stress enhances the response to an inflammatory stimulus by a mechanism that is independent of the release of hypothalamic corticotropin-releasing factor (CRF) or arginine vasopressin. Putative mechanisms include an increase in intestinal permeability as well as the release of the proinflammatory neuropeptide substance P. Stress may also reactivate previous inflammation when applied in conjunction with a small luminal stimulus. This reactivation involves increased permeability and requires the presence of T lymphocytes. Inflammatory mediators activate hypothalamic pathways, and a negative feedback loop, mediated by CRF release, has been proposed because animals with impaired hypothalamic CRF responses are more susceptible to inflammatory stimuli. Together, these experimental observations provide insights into the expression of inflammatory disorders in humans, including inflammatory bowel disease and postinfective irritable bowel syndrome.
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PMID:Stress and the Gastrointestinal Tract IV. Modulation of intestinal inflammation by stress: basic mechanisms and clinical relevance. 1117 12

Corticotropin-releasing hormone (CRH) is an important regulator of inflammation at the central level through hypothalamo-pituitary-adrenal (HPA) axis control of glucocorticoid secretion. Integrity of the HPA axis during autoimmune disease is critical in controlling the severity of inflammation, but the evidence for an HPA axis defect in the etiology of autoimmune diseases is not compelling. CRH secreted from leukocytes and neuronal terminals in peripheral tissues also plays a role in mediating inflammation. Elucidating the pathways underlying the expression of CRH, both central and peripheral, and interactions of CRH with other inflammatory mediators such as substance P, confers great potential for the development of a new generation of anti-inflammatory agents.
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PMID:CRH in chronic inflammatory stress. 1133 94

The skin surface electric potential has been widely used for psychological studies because it is sensitive to emotional conditions. We measured the electric potential on the surface of hairless mice skin in organ culture with several physiological factors. Disruption of mitochondrial function and inhibition of ATPase reduced the skin surface potential 50-70%. Calcium, potassium, and sodium channel blockers also reduced the potential. A calcium-specific and potassium ionophore reduced the potential, but the calcium and magnesium ionophore increased it. EDTA decreased the potential but EGTA had no effect. Skin surface barrier disruption reduced the potential and calcium and potassium channel blockers partially prevented the decrease. Substance P and corticotropin-releasing factor decreased the potential, and antagonists blocked the decreases. These results suggest that the ion flux in the nucleated layer of the epidermis induce the skin surface potential and it is influenced by environmental and neuroendocrinological factors.
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PMID:Skin surface electric potential induced by ion-flux through epidermal cell layers. 1137 79


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