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)

Excitotoxin lesions induced by quinolinic acid (QA) were made unilaterally in the caudate nucleus and putamen of 12 rhesus monkeys. Both acute (2-3 weeks) and chronic (4-6 months) effects were evaluated. Excitotoxin striatal lesions were characterized by a central zone of intense astrogliosis and marked neuronal depletion, which was surrounded by a transition zone in which there was partial neuronal sparing throughout the entire lesioned side. Immunocytochemical and enzyme histochemical markers for both large and medium-sized aspiny- and spiny-striatal neurons clearly demonstrated a selective pattern of neuronal vulnerability to the excitotoxic effects of QA within lesioned striata. Medium-sized spiny neurons containing calbindin Dk28, enkephalin, and substance P were disproportionately lost, while aspiny neuronal subpopulations containing NADPH diaphorase (NADPH-d) and choline acetyltransferase activity (ChAT) were relatively spared. Combined labeling by NADPH-d enzyme histochemistry and Nissl staining, as well as NADPH-d histochemistry and calbindin Dk28 immunocytochemistry, demonstrated significant increases in the ratio of aspiny to spiny neurons within the lesioned striata. Neurochemical measurements confirmed a loss of GABA and substance P-like immunoreactivity yet no significant depletion of somatostatin-like immunoreactivity, neuropeptide Y-like immunoreactivity, or ChAT were seen. The striatal patch-matrix pattern persisted, as demonstrated by acetylcholinesterase activity. The pattern was altered, however, in the chronic animals, such that the matrix zone was significantly reduced, while the total area of patches remained within normal limits. Ultrastructural analysis confirmed axon sparing lesions with neuronal loss and astrogliosis. Pretreatment of 3 monkeys with MK-801, a noncompetitive N-methyl-D-aspartate (NMDA) antagonist, blocked striatal QA neurotoxicity. The present results provide an experimental primate model which closely resembles the neuropathologic and neurochemical features of Huntington's disease. These findings further strengthen the possibility that an NMDA receptor-mediated excitotoxic process plays a role in the pathogenesis of this disorder.
 ...
PMID:Excitotoxin lesions in primates as a model for Huntington's disease: histopathologic and neurochemical characterization. 843 51

Quantitative measurements of relative nerve density were achieved using computer-assisted image analysis of immunohistochemically and histochemically defined nerves in the conduction system of the guinea pig heart. All regions of the conduction system possessed a similar density of nerve fibres and fascicles displaying immunoreactivity for the general neuronal marker protein gene product 9.5 (PGP 9.5), and this was 3 to 4-fold higher than in the adjacent myocardium. Acetylcholinesterase (AChE) positive and tyrosine hydroxylase (TH)-immunoreactive nerves were the main subtypes identified in the sinus and atrioventricular nodes, representing 40-45% of the stained area occupied by PGP 9.5-immunoreactive nerves. AChE-positive nerves were the dominant subtype identified in the left and right bundle branches, but were equal in proportion to TH-immunoreactive nerves in the penetrating bundle. Neuropeptide Y-immunoreactive nerves represented the main peptide-containing subpopulation in the nodal tissues, displaying a similar pattern of distribution and relative density to those nerves demonstrating TH immunoreactivity. Substance P and calcitonin gene-related polypeptide immunoreactive nerves were present throughout the conduction system and represented the main peptide-containing subpopulation in the ventricular conduction tissues. Nerve fibres showing immunoreactivity for either somatostatin or vasoactive intestinal polypeptide exhibited distinct patterns of distribution and comprised a relatively minor component of the innervation. The innervation of the guinea pig conduction tissues thus exhibits a uniform distribution and it comprises putative parasympathetic nerves and intrinsic neurons (AChE positive), sympathetic efferent nerves (NPY and TH-immunoreactive nerves) as well as other peptide-containing nerves, some of which (substance P and calcitonin gene-related polypeptide) are considered to represent afferent nerves. The distribution and density of nerve subpopulations in the guinea pig conduction system differ from those observed in the human conduction system, which suggests that the guinea pig may be an inappropriate model for comparative functional studies.
 ...
PMID:A quantitative study of nerve distribution in the conduction system of the guinea pig heart. 862 40

Growth hormone (GH) plasma levels reflect a balance between stimulation via GH-releasing hormone (GHRH) and inhibition by somatostatin (SS). Steroids influence GH secretion by modulating SS tone. There is a correlation between the diurnal secretion of GH and cortisol (CORT). Pyridostigmine, the acetylcholinesterase inhibitor, increases cholinergic tone, inhibits SS release and increases the release of GH. We investigated the influence of CORT on pyridostigmine-induced GH responses by testing subjects at 9.00 and 14.00 h. Basal (mean +/- SEM) CORT levels at 9.00 and 14.00 h were 251.5 +/- 18.4 nmol/l and 142.7 +/- 6.7 nmol/l, respectively. Pyridostigmine-induced GH responses were greater at 9.00 h than at 14.00 h (8.7 +/- 1.5 mU/l; 3.0 +/- 1.0 mU/l, respectively, [ p < 0.001]). A positive correlation between CORT and delta GH values was demonstrated (p < 0.0004).
 ...
PMID:Time dependency of pyridostigmine-induced growth hormone response. 873 43

The present study reveals the presence of a distinct group of cells, resembling reticular thalamic neurones, in the internal capsule during fetal development. This cell population rapidly decreases in size during early infancy and few cells are apparent in the 1-year-old infant. Internal capsule cells are well differentiated, multipolar or polymorphous, AChE (acetylcholinesterase)-reactive neurones. The following specific molecular markers were demonstrated in the neurones of the internal capsule: MAP2 (microtubule-associated protein 2), somatostatin, calbindin-D28K and p75 low-affinity NGF (nerve growth factor) receptor. A group of neurones described here corresponds to the perireticular thalamic nucleus found in certain mammalian species, hitherto unidentified in the primate brain, which may play an important role during development.
 ...
PMID:Transient neuronal population of the internal capsule in the developing human cerebrum. 893 Sep 80

Insulin-dependent (type I) diabetic patients are known to have an exaggerated growth hormone (GH) response to GH-releasing hormone (GHRH), which is hypothesized to be due to a decrease in somatostatin tone. The aim of the study was to ascertain the influence of the presence and activity of the autoimmune process involving a key enzyme (glutamic acid decarboxylase [GAD]) in the synthetic pathway of a neurotransmitter regulating somatostatin secretion, ie, gamma-aminobutyric acid (GABA), on the GH response to GHRH alone or combined with an acetylcholinesterase inhibitor, pyridostigmine (PD), in patients with type I diabetes mellitus. Twenty non-obese type I diabetic patients and 17 normal subjects underwent an intravenous (IV) injection of 100 micrograms GHRH(1-29)NH2. Twelve of 20 diabetic subjects and all of the control subjects also underwent a second experimental procedure, administration of 120 mg oral PD 60 minutes before IV injection of 100 micrograms GHRH. Diabetic subjects with serum GAD antibody (GADA) levels more than 3 U (n = 10) showed significantly higher serum GH levels after GHRH injection as compared both with diabetic patients with GADA less than 3 U (n = 10) and with normal controls, whether expressed as absolute or peak values. GH peaks after GHRH were significantly (rs = .46, P < .05) correlated with the level of GADA in the whole population of type I diabetic subjects studied. PD significantly enhanced the GH response to GHRH, in terms of both absolute and peak values, in patients without GADA (n = 6) and in normal subjects. On the contrary, PD failed to enhance the GH response to GHRH in diabetic patients with GADA (n = 6). Our findings suggest that autoimmunity may play a key role in determining the exaggerated GH response to GHRH in type I diabetes mellitus. The mechanism underlying this effect is hypothesized to be the production of antibodies to GAD, a key enzyme in the synthesis of GABA, and in turn a reduced GABAergic stimulatory tone on somatostatin production at the hypothalamic level.
 ...
PMID:Glutamate decarboxylase autoimmunity and growth hormone secretion in type I diabetes mellitus. 910 40

Neuropeptide Y is one of the most powerful neurochemical stimulants of food intake known. The neuronal substrate for this action is believed to be the neuropeptide Y-expressing cell population in the hypothalamic arcuate nucleus. In this study, mice homozygous for the anorexia mutation (anx) were investigated histochemically; anx is a recessive mutation that causes decreased food intake and starvation, leading to death 22 days after birth. We were interested to see whether any hypothalamic neurochemical abnormalities could be detected in this genetic model of starvation. By using immunohistochemistry and in situ hybridization, the hypothalamic distributions of neuropeptide Y, cholecystokinin, galanin, and serotonin, all messenger molecules postulated to be involved in the regulation of food intake and energy metabolism, were investigated. Immunoreactivities for somatostatin, the excitatory amino acid aspartate, and acetylcholinesterase were also studied. Neuropeptide Y-like immunoreactivity was increased markedly in arcuate cell bodies and decreased in terminals in the arcuate nucleus and other hypothalamic regions of anx/anx mice compared with normal litter mates. In situ hybridization for neuropeptide Y mRNA, however, showed no significant difference in gene expression in the arcuate nucleus. In addition, immunoreactivities for aspartate, acetylcholinesterase, and somatostatin in the arcuate nucleus were decreased in anx/anx mice. For cholecystokinin, galanin, and serotonin, no certain differences in hypothalamic immunoreactivity could be seen. These data suggest that a defect in neuropeptide Y-ergic signalling in the arcuate neurons may contribute to the failure to thrive in anx/anx mice.
 ...
PMID:Hypothalamic neurohistochemistry of the murine anorexia (anx/anx) mutation: altered processing of neuropeptide Y in the arcuate nucleus. 933 Nov 76

Degeneration of the cholinergic basal forebrain (CBF) and changes in cortical neuropeptide levels have been reported in Alzheimer's disease. In the present study, we sought to determine if a selective cholinergic lesion of nucleus basalis magnocellularis (Nbm) could affect the number and distribution of neuropeptide Y (NPY) and somatostatin (SS) immunoreactive neurons in the frontoparietal and occipital cortices of rats. Brain sections were evaluated at survival times of 1, 2, 4, 8, 12, 24, 48, 78 and 100 weeks after intraventricular injection of 192-saporin, an immunotoxin directed at the low affinity neurotrophin receptor (p75NGFr), that selectively destroys the CBF. Following the immunotoxin lesion of the Nbm, the number of NPY-labeled neurons decreased 33% in the frontoparietal cortex and 60% in the occipital cortex compared to age-matched normal controls at most survival time points. A significant loss of SS-labeled neurons in both cortical regions was seen 12 weeks after 192-saporin injection with no further change up to 100-week survival time. The effect of age on neuropeptidergic populations was evaluated in normal control rats. The number of NPY and SS immunoreactive neurons in aged rats (21-26 months) decreased by 42% in the frontoparietal cortex and 27% in the occipital cortex when compared with young (3-6 months) and middle-age (9-14 months) rats. When both non-lesioned and lesioned animals with different ages were pooled for linear regression, a significant correlation was found between the number of cortical NPY- and SS-labeled neurons and cortical acetylcholinesterase (AChE) histochemical staining intensity. These findings indicate that: (1) cholinergic denervation of the Nbm is associated with an irreversible loss of neocortical NPY and SS immunoreactive neurons analogous to that observed in Alzheimer's disease and aging; (2) the degree of the loss of cortical NPY and SS immunoreactive neurons seems to be related to the extent of the reduction of cortical AChE intensity in both toxin-injected and normal aged rats. These findings may reflect a trophic dependence of NPY and SS neurons on cortical cholinergic input.
 ...
PMID:Selective lesion of the cholinergic basal forebrain causes a loss of cortical neuropeptide Y and somatostatin neurons. 968 41

The motor innervation of the smooth muscle coat of the human vas deferens is predominantly noradrenergic in type while a less dense and differently distributed presumptive cholinergic innervation is also in evidence, although the precise role of the latter is undetermined. Immunohistochemical studies have confirmed the presence of catecholamine-synthesizing enzymes tyrosine hydroxylase (TH) and dopamine beta hydroxylase (DbetaH) in the majority of fine, varicose intramuscular nerves, about two-thirds of which also contain neuropeptide Y (NPY). Minor populations of noradrenergic nerves contain enkephalin (ENK), galanin (GAL), somatostatin (SOM), or nitric oxide synthase (NOS). The presumptive cholinergic intramuscular nerves contain vasoactive intestinal polypeptide (VIP) and NPY. The subepithelial nerves of the vas deferens are assumed to have a secretomotor function and are rich in acetylcholinesterase and NPY, many also containing either VIP or NOS. The muscle coat of the human vas deferens is poorly differentiated until after birth, the intramuscular nerves in the fetus being relatively thick and non-varicose. Development of a subepithelial nerve plexus lags behind that in the muscle coat but its density in the neonatal vas deferens resembles that seen in the adult. Observations on specimens of human vas deferens obtained at vasovasostomy carried out 1 to 15 years after vasectomy have shown a marked reduction in the density of noradrenergic nerves in the muscle coat of the testicular portion while that in the urethral portion remains unaltered. Furthermore, the subepithelial secretomotor nerves degenerate in the testicular portion. These long-term changes in the pattern of innervation of the vas deferens consequent upon vasectomy may have profound effects upon the outcome of vasovasostomy with respect to subsequent sperm maturation, transport, and viability.
 ...
PMID:Structure and autonomic innervation of the human vas deferens: a review. 981 49

Gastrointestinal motility disorders are of considerable clinical importance in humans and animals. Abnormalities of smooth muscle and the enteric nervous system have been described. We have identified and characterized a new mutant stock of rats that develops severe megacecum and colon with pseudo-obstruction, Familial Megacecum and Colon (FMC). The inheritance pattern of FMC was characterized by selective breeding. Gastrointestinal motility was evaluated radiographically. Complete pathologic evaluations, including ultrastructural examination and staining of colonic segments for acetylcholinesterase, peripherin, vasoactive intestinal peptide, substance P, nitric oxide synthase, and somatostatin, were performed. Spontaneous contractility and contractile force in isolated colonic muscle strips were examined. Familial megacecum and colon is inherited as an autosomal recessive trait. The markedly dilated cecum and proximal portion of the colon are followed by a short, funnel-shaped segment and distal portion of the colon with normal or slightly reduced lumen. Although clinical features and gross anatomic changes of the colon resemble those of Hirschsprung's disease in humans and animals, aganglionosis is not a feature of FMC. An increase in somatostatin staining was observed in dilated regions of bowel. The spontaneous contractile frequency and contractile force were diminished in the affected colon. Familial megacecum and colon is a new mutant, distinct from previously described hereditary and targeted mutant rodent models that develop megacecum and colon as a result of distal colonic dysfunction. The functional or morphologic defect(s) that result in colonic dysfunction in rats with FMC was not determined. The disease may result from an absence or overexpression of a single or group of neurotransmitters or their respective neurons, receptor abnormalities, or defects in the intestinal pacemaker system.
 ...
PMID:Familial megacecum and colon in the rat: a new model of gastrointestinal neuromuscular dysfunction. 1009 23

Animal experiments have already shown that neurotransmitters and neuropeptides are not only important for normal functioning of the adult central nervous system (CNS) but are also crucial to its development. However, information on the spatio-temporal distribution of these endogenous substances in the developing human CNS is still scarce. With the use of immunocytochemical staining and a constant supply of properly fixed human abortuses from southern China, an early appearance of acetylcholinesterase, enkephalin, and substance P immunoreactivities was detected first in the spinal cord (weeks 5 to 7 of gestation), then in the brainstem nuclei (weeks 11 to 12). Their overlapping localizations in many regions of the CNS suggest possible interactions among neurons containing these substances, which are in turn important for the proper establishment of the neuronal circuitry. Immunoreactivity for neuropeptide Y appeared initially in the lateral region of upper segments of the spinal cord at week 12 of gestation, then spread latero-medially and cranio-caudally to the sacral region. In the hippocampus, neuropeptide Y neurons appeared from week 15 onwards. Serotoninergic neurons were found in the dorsal raphe nucleus at week 10 and then decreased in number as the fetus grew older. Somatostatin releasing inhibitory factor, vasopressin, and oxytocin were detected in the hypothalamus from weeks 12 to 14 onwards, and monoamine oxidase, succinic dehydrogenase, parvalbumin, calbindin D28K, and vasoactive intestinal peptide were found in the visual cortex at midgestation. The early appearance and the abundance of the neurotransmitters and neuropeptides in the developing CNS indicate that they may play a key role in neuronal differentiation.
 ...
PMID:Early appearance of acetylcholinergic, serotoninergic, and peptidergic neurons and fibers in the developing human central nervous system. 1040 66


<< Previous 1 2 3 4 5 6 7 8 9 10