Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have measured the concentrations of substance P, somatostatin, homovanillic acid (HVA), vanillyl mandelic acid (VMA) and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) of six patients suffering from narcolepsy and 12 age- and gender-matched controls using high pressure liquid chromatography (HPLC) and radioimmunoassay (RIA). Substance P and somatostatin were significantly decreased in our patients compared to controls (36.9 +/- 9.1 fmol/ml versus 52.5 +/- 9.9 fmol/ml, P < 0.05 and 30.3 +/- 7.8 fmol/ml versus 43.9 +/- 9.8 fmol/ml, P < 0.05, respectively). 5-HIAA (P < 0.05) and VMA (P < 0.05) were also significantly decreased. HVA was significantly increased (P < 0.01). The CSF concentrations of substance P and somatostatin correlated with the clinical parameters duration of disease (r = -0.68, P < 0.05 and r = -0.72, P < 0.05, respectively) and severity of cataplectic symptoms (r = -0.71, P < 0.05 and r = -0.78, P < 0.01). In addition, substance P correlated with the intensity of sleepiness and the frequency of day-sleep attacks (r = -0.69, P < 0.05 and r = -0.68, P < 0.05, respectively). Substance P affects the amount of dopamine release in the nigra-striatal region, and decreased amounts could contribute to the pathogenesis of narcolepsy. Reduced levels of substance P, which affects serotonin release, may be responsible for diminished release of serotonin which in turn could affect sleep cycles. Because somatostatin affects motor behavior through dopaminergic mechanisms and since the levels of somatostatin correlate with the intensity of cataplectic symptoms, we speculate that an interaction between somatostatin and dopaminergic neurons plays a role in the pathogenesis of narcolepsy.
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PMID:CSF substance P somatostatin and monoaminergic transmitter metabolites in patients with narcolepsy. 894 37

A few examples of hypothalamic, peptidergic disorders leading to clinical signs and symptoms are presented in this review. Increased activity of corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus (PVN) and decreased activity of the vasopressin neurons in the biological clock and of the thyroxine-releasing hormone (TRH) neurons in the PVN contribute to the signs and symptoms of depression. In men, the central nucleus of the bed nucleus of the stria terminalis (BSTc) is about twice as large and contains twice as many somatostatin neurons as in women. In transsexuals this sex difference is reversed, pointing to a role of this structure in gender. Luteinizing hormone-releasing hormone (LHRH) neurons are formed in the fetal olfactory placade and migrate along the terminal nerve fibers into the hypothalamus. In Kallmann's syndrome the migration process of the LHRH (gonadotropin-releasing hormone) neurons is aborted, which explains the joint occurrence of hypogonadotropic hypogonadism and anosmia in this syndrome. In postmenopausal women, the neurons of the infundibular nucleus hypertrophy and become hyperactive because of the disappearance of the estrogen feedback and contain hyperactive peptidergic neurons. Climacteric flushes may be caused by hyperactivity of the neurokinin-B or LHRH neurons in this nucleus. The hypocretin (orexin) neurons in the perifornical area are involved in sleep. In narcolepsy with cataplexy, a loss of these neurons, probably due to an autoimmune process, is found. Obese subjects with a mutation in the gene that encodes for leptin, the preproghrelin gene, or the alpha-melanocyte-stimulating hormone (alpha-MSH) gene have been described. Decreased numbers and activity of the oxytocin neurons in the PVN may be responsible for the absence of satiety in Prader-Willi syndrome. Moreover, a glucocorticoid receptor polymorphism is associated with obesitas and dysregulation of the hypothalamus-pituitary-adrenal axis. In contrast, two single nucleotide polymorphisms (SNPs) of the AGRP gene have been associated with anorexia nervosa.
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PMID:Neuropeptides in hypothalamic neuronal disorders. 1554 16

A bidirectional interaction exists between the electrophysiological and neuroendocrine components of sleep. The first is represented by the nonrapid eye movement sleep (NREMS) and rapid eye movement sleep (REMS) cycles, the latter by distinct patterns of the secretion of various hormones. Certain hormones (neuropeptides and steroids) play a specific role in sleep regulation. Changes in their activity contribute to the pathophysiology of sleep disorders. A reciprocal interaction of the peptides growth hormone-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) plays a key role in sleep regulation. GHRH promotes growth hormone secretion and, at least in males, NREMS, whereas CRH impairs NREMS, promotes REMS and stimulates the secretion of adrenocorticotropic hormone and cortisol. Changes in the CRH:GHRH ratio in favor of CRH contribute to impaired sleep, elevated cortisol secretion and blunted GH levels during depression and normal aging. However, in women, GHRH exerts CRH-like effects. Galanin, ghrelin and neuropeptide Y are other sleep-promoting peptides, whereas somatostatin impairs sleep. A decline of orexin activity causes narcolepsy. In addition to CRH overactivity, hypercortisolism appears to be involved in the pathophysiology of sleep- electroencephalogram (EEG) changes in depression. Various neuroactive steroids exert specific effects on sleep. The changes of sleep EEG in women after the menopause are related to the decline of estrogen and progesterone. Furthermore, sleep-EEG changes in dwarfism, acromegaly, Addison's disease, Cushing's disease, brain injury, sleep apnea syndrome, primary insomnia, prolactinoma and dementia appear to be related to changes in the activity of peptides and steroids.
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PMID:Roles of peptides and steroids in sleep disorders. 3075 93