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

In order to explore the mechanisms by which free fatty acids (FFA) inhibit GH secretion, we studied the effect of the acetylcholinesterase inhibitor pyridostigmine (120 mg p.o.) on the FFA blockade of GH responses to the administration of GHRH (100 micrograms i.v.) in seven normal subjects. GHRH-induced GH secretion was significantly reduced following elevation of circulating FFA levels by lipid-heparin infusion and significantly potentiated by previous pyridostigmine treatment. Peak GH levels following combined administration of pyridostigmine plus lipid-heparin plus GHRH were significantly higher (P less than 0.01) than after GHRH alone and significantly lower than after pyridostigmine plus GHRH (P less than 0.01). In conclusion, central cholinergic activation by pyridostigmine, with the presumed reduction in somatostatin discharge, reversed the blocking effect of FFA on GHRH-stimulated GH release. Conversely, FFA were able to reduce even a maximal GH stimulation by pyridostigmine plus GHRH.
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PMID:Role of cholinergic muscarinic pathways on the free fatty acid inhibition of GH responses to GHRH in normal men. 222 76

In the present study we investigated the effects of the acetylcholinesterase inhibitor pyridostigmine (PD), which is hypothesized to decrease hypothalamic somatostatin tone, alone and in association with GH-releasing hormone (GHRH) on GH secretion in 18 type 1 diabetic patients and 12 normal subjects using a randomized double blind placebo-controlled protocol. All subjects received either 120 mg oral PD or placebo 60 min before iv injection of either human GHRH-(1-29) NH2 (100 micrograms) or sterile water (2 mL). In normal subjects both PD alone and GHRH alone caused a significant increase in GH. PD and GHRH acted in a synergistic fashion when combined. In diabetic patients the GH response to GHRH was variable. To segregate the responses, the ratio between the GH increase after GHRH plus PD and after GHRH alone was calculated for each subject. In 10 diabetic patients (group A) the ratio was lower than 2 SD (P less than 0.05) from the mean response of normal subjects. These patients showed an exaggerated GH increase after GHRH and a lower GH increase after PD with respect to normal subjects. Eight diabetic patients (group B) showed a ratio similar to that in normal subjects and similar GH responses to the stimuli. No significant differences were found between groups A and B with respect to age, body mass index, and blood glucose levels. Duration of diabetes was longer and basal GH levels were higher in group A. Hemoglobin-A1c was higher in group A, but of only borderline statistical significance (P = 0.052). Our data demonstrate that in diabetic patients with exaggerated GH responses to GHRH an increase in cholinergic tone does not affect GH secretion. These data suggest that in some type 1 diabetic patients an altered somatostatinergic control of GH secretion may contribute to their abnormal GH response to GHRH.
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PMID:Impaired growth hormone (GH) response to pyridostigmine in type 1 diabetic patients with exaggerated GH-releasing hormone-stimulated GH secretion. 222 5

Knowledge about the distribution and origins of peptide-containing nerves in the innervated and transplanted heart is lacking. Immunohistochemical and histochemical techniques were used to visualize human cardiac innervation before and after transplantation. In the recipient heart cardiac nerve fibers and fascicles displayed immunoreactivity for general neural (protein gene product 9.5 and synaptophysin) and Schwann cell markers (S-100). A major proportion of cardiac nerves displayed neuropeptide tyrosine and tyrosine hydroxylase immunofluorescence staining. Subpopulations of nerves contained somatostatin, vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P- or neurokinin-like immunoreactivity, and acetylcholinesterase activity. Tissues from cardiac allografts (5 weeks to 63 months after transplantation) contained nerves and ganglion cells that were acetylcholinesterase positive and immunoreactive for the general neural markers. These nerves were less numerous than in recipient hearts and rarely displayed neuropeptide immunostaining. Atrial natriuretic peptide immunoreactivity was localized to myocardial cells in transplanted hearts as well as explanted recipient and postmortem hearts. While most human cardiac allografts remain functionally extrinsically denervated, they appear to contain viable intrinsic nerves, and myocardial cells retain the capacity to produce atrial natriuretic peptide.
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PMID:Immunohistochemical demonstration of human cardiac innervation before and after transplantation. 231 94

Hippocampal CA3 neurons from fetal rats were grafted to excitotoxic lesions in the CA3 subfield of the adult rat hippocampus and the formation of graft-host brain nerve connections examined. The excitotoxic lesions were induced by localized, stereotaxic injection of ibotenic acid (IA), a glutamic acid agonist, into CA3 of the dorsal hippocampus. The result was a so-called axon-sparing lesion with localized degeneration of nerve cells, but preservation of the extrinsic afferent fibers, now deprived of their targets. One week after the lesion a suspension of embryonic (E18-20) CA3 cells was grafted to the lesion site. Six weeks or more later the recipient brains were processed and analyzed by ordinary cell stains, histochemistry for acetylcholinesterase (AChE) and heavy metals (Timm staining), immunohistochemistry for the neuropeptides cholecystokinin and somatostatin and glial fibrillary acidic protein (GFAP) for astroglia, electron microscopy, and axonal tracing with retrogradely axonal transported fluorescent dyes or lesion-induced, anterograde degeneration combined with silver staining or electron microscopy. More than 90% of the grafts survived. They contained the normal types of CA3 neurons, which are mainly pyramidal cells, in addition to some normal, peptidergic, cholecystokinin- and somatostatin-reactive neurons. The grafts were innervated by AChE-positive, host cholinergic fibers, Timm-positive mossy fiber terminals from the host fascia dentata, and host commissural fibers traced by axonal degeneration. Efferent transplant projections were traced to the ipsilateral host CA1 (Schaffer collaterals) and the contralateral host hippocampus by retrograde axonal transport of fluorochromes injected into these host brain areas. All grafts analyzed by electron microscopy contained axonal varicosities resembling axonal growth cones even after long survival times. The results demonstrate that fetal rat hippocampal neurons, grafted to excitotoxic, axon-sparing lesions in the adult brain, can become both structurally and connectively well incorporated in the mature host central nervous system.
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PMID:Grafting of fetal CA3 neurons to excitotoxic, axon-sparing lesions of the hippocampal CA3 area in adult rats. 239 68

Acetylcholinesterase (AChE)-positive neurons were counted in the different layers of the rostral (septal) third, the middle third and the caudal (temporal) third of the hippocampus from 3 month (young) and 27 month old rats (aged) using AChE stained cryostat sections. The rats were treated with 3 and 2.5 mg of diisopropylphosphofluoridate/kg body weight, respectively 3 h before sacrifice. The study showed -1) a high numerical density of AChE-positive neurons (10.9 to 18.9 perikarya/mm2) in the hilus (fascia dentata), the str. oriens/pyramidale of CA1 and the subiculum, a particularly low density (less than 0.1 perikarya/mm2) in the str. granulosum and moleculare of the dentate area; -2) a significant (p less than 0.05) linear increase of the numerical density in most of the hippocampal layers from the rostral to the caudal pole; -3) no significant differences between young and aged animals; - and 4) a higher sensitivity to DFP-treatment in aged than in young animals. The distribution of AChE-positive neurons corresponds with the distribution of somatostatin-immunoreactive neurons described in the literature. A modulatory effect on neurotransmission is discussed as a possible function of the AChE in peptidergic neurons.
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PMID:Quantitative distribution of AChE-positive neurons in the hippocampus of young and aged rats. 239 23

The distribution of dihydronicotinamide adenine dinucleotide phosphate diaphorase (NADPH diaphorase) was studied by enzyme histochemistry in the striatum of the adult cat. Neurons and neuropil expressing NADPH diaphorase activity were found throughout the striatum. The diaphorase-positive neurons formed a sparse population of medium-sized cells. In the caudate nucleus they were recognized by antisera against somatostatin 14, somatostatin 28(1-12), neuropeptide Y and avian pancreatic polypeptide. The diaphorase activity of the striatal neuropil was characterized by a modular organization that was particularly distinct in the caudate nucleus. This organization was analyzed by comparing the patterns of diaphorase staining with the distribution of acetylcholinesterase activity in adjacent sections. The NADPH diaphorase activity was found to be dense in the acetylcholinesterase-rich matrix of the caudate nucleus, but weak in the acetylcholinesterase-poor compartments known as striosomes. Because of the colocalization of perikaryal NADPH diaphorase activity and somatostatinlike immunoreactivity, a comparison was also made between the distribution of diaphorase staining and immunostaining for somatostatinlike peptide in the striatal neuropil. Both observed striosomal ordering, so that the acetylcholinesterase-poor zones detected in adjoining sections corresponded to regions of low somatostatinlike immunoreactivity as well as low NADPH diaphorase staining. In some regions striosomes were more clearly delineated in the stains for diaphorase and somatostatinlike suggest that NADPH diaphorase may be a sensitive marker for the somatostatinergic neuropil as well as the somatostatinergic perikarya of the striatum, and that this enzyme could prove valuable in attempts to differentiate the processes of intrinsic somatostatin-containing fibers from any extrinsic somatostatin afferents that may exist.
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PMID:A new enzyme marker for striatal compartmentalization: NADPH diaphorase activity in the caudate nucleus and putamen of the cat. 241 68

Histochemical methods have been used to study the distribution of putative neurotransmitters in the urinary bladder of newborn guinea-pigs and in cultures of intramural ganglia. Following the nicotinamide adenine dinucleotide (NADH)-diaphorase reaction which specifically labels nerve cell bodies, up to 66 ganglia were observed in stretch preparations of the newborn urinary bladder. Each ganglion contained 2-50 nerve cell bodies. Vasoactive intestinal polypeptide was localized in a few nerve cell bodies of intramural ganglia both in in situ and culture preparations. In the in situ preparations it was widely distributed in nerve fibres to the muscle, being most dense at the base of the bladder, and in some mucosal epithelial cells. Somatostatin was contained in numerous neuronal cell bodies in the detrusor muscle both in situ and in culture. Extensively distributed varicose fibres were found in culture and in the muscle, submucous and mucosal layers in situ. Substance P immunofluorescence was demonstrated in a few neuronal cell bodies in ganglia both in situ and in vitro, particularly in those of the mucosa at the base of the bladder. In the in situ preparations varicose nerve fibres containing substance P were seen in the muscle coats with greatest density in the bladder base. Met-enkephalin-immunoreactive nerve cell bodies were not seen either in situ or in culture. Nerve fibres in in situ preparations were found largely enveloping neuronal cell bodies within the ganglia. Neither serotonin-immunoreactive nor catecholamine-containing neuronal cell bodies were seen in the in situ bladder preparation. However, some nerve cell bodies in culture showed positive staining, possibly as a result of selective uptake of serotonin and catecholamine known to be contained in foetal calf serum in the culture medium or possibly as the result of increased synthetic activity in certain neurones in the culture situation. In whole-mount stretch preparations, no serotonin-immunoreactive nerve fibres were seen, but catecholamine-containing small intensely fluorescent cells and nerve fibres were observed. Acetylcholinesterase-positive nerve cell bodies and nerve fibres were observed both in in situ and culture preparations of the bladder. Quinacrine-positive nerve cell bodies (as an indicator of purinergic neurones) were found in numerous intramural neurones examined. in situ; however, under the culture conditions used, non-selective staining of all cell types occurred.
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PMID:Intramural neurons of the guinea-pig urinary bladder: histochemical localization of putative neurotransmitters in cultures and newborn animals. 242 42

Neurons expressing immunoreactivity to antisera against somatostatin 14 and other somatostatin-related peptides were identified in the striatum of cats and nonhuman primates. In each species, immunoreactive neurons were distributed singly and in small groups in the caudate nucleus, putamen and ventral striatum. A detailed study was made of somatostatin-positive neurons and neuropil in the caudate nucleus of the cat. First, the mean diameters and surface areas of neurons expressing immunoreactivity to somatostatin 14 were made from peroxidase-antiperoxidase stained material. Second, fluorescence immunohistochemistry was combined with retrograde labeling of striatal neurons to determine whether such somatostatin 14-positive neurons emit axons projecting out of the striatum. Third, the distributions of neurons and neuropil expressing immunoreactivity to somatostatin 14 or somatostatin 28 (1-12) were plotted in relation to the locations of acetylcholinesterase-poor zones ("striosomes") visible in adjoining sections. The morphometric analysis suggested that somatostatin 14-positive neurons in the caudate nucleus form a single population of medium to medium-large neurons having mean diameters of 20 micron and mean surface areas of 154 micron2. The retrograde tracer study suggested that these somatostatin 14-positive neurons are interneurons. Injections of fast blue into all of the known targets of striatofugal fiber projections failed to label somatostatin 14-positive neurons save in a few instances (less than 0.3% of more than 4000 neurons) in each of which labeling was equivocal. Analysis of the distribution of somatostatin-positive neurons and neuropil in the striatum demonstrated that both observe striosomal ordering. Somatostatin immunoreactive neuropil was dense outside and weak inside identified striosomes, and most immunoreactive neurons lay outside. Often somatostatin-positive neurons lay beside, and sometimes striosomes partly rimmed them. The processes of such neurons tended to run along the borders of the striosomes without crossing them, but occasionally single processes and rarely entire dendritic trees crossed from one compartment to the other. These results suggest that, in the striatum of the cat, somatostatin is present: (1) in fibers organized according to the compartmental distribution already recognized for other neurochemical compounds in the striatum as well as for its afferent and efferent systems, and (2) in interneurons, mostly present in the extrastriosomal matrix, but also located near striosomes, where they could serve as interfaces between the striosomes and extrastriosomal matrix.
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PMID:Striatal neurons expressing somatostatin-like immunoreactivity: evidence for a peptidergic interneuronal system in the cat. 242 90

The frequency of occurrence of the adrenergic, cholinergic, 5-hydroxytryptamine (5-HT)-, substance P (SP)-, methionine-enkephalin (met-Enk)- and somatostatin (SOM)-immunoreactive fibres innervating the smooth muscle of the large intestine in Hirschsprung and control children was compared. It was observed a higher frequency of catecholamine-fluorescence, acetylcholinesterase-positive and SOM-immunoreactive fibres in the muscularis externa and muscularis mucosa of the aganglionic segment in Hirschsprung gut as compared to that in the sigmoid colon and rectum in controls. In contrast, the frequency of SP-, met-Enk- and 5-HT-immunoreactive fibres in the aganglionic segment in Hirschsprung gut was lower than that in the controls. Ultrastructurally the cholinergic and adrenergic fibres occurred more often in the aganglionic segment in Hirschsprung gut than in the controls. A treatment with 6-OHDA and a fixation by Tranzer and Richards technique was used to confirm the nature of the adrenergic fibres. The p-type fibres occurred infrequently in the aganglionic segment of Hirschsprung gut. The results suggest that the change in the frequency of the nerves containing inhibitory transmitters may play an important role in the pathogenesis of Hirschsprung's disease.
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PMID:Histochemical, immunocytochemical and ultrastructural data on the innervation of the smooth muscle of the large intestine in Hirschsprung's disease. 242 97

Acetylcholinesterase, somatostatin-like immunoreactivity, and homovanillic acid levels were measured in the cerebrospinal fluid of 36 patients with early stages of Parkinson's disease and in 19 control patients. In patients with Parkinson's disease the levels of somatostatin-like immunoreactivity were lower than in the controls (p less than 0.01); these values were lowest in the demented Parkinsonian patients. Concentrations of homovanillic acid were also significantly lower in Parkinsonian patients (p less than 0.05). In contrast, no changes were observed in the acetylcholinesterase activity of patients with Parkinson's disease. The reduced somatostatin-like immunoreactivity in CSF agrees with previous post-mortem studies and indicates that Parkinson's disease and Alzheimer's disease may have some neurochemical features in common.
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PMID:Somatostatin-like immunoreactivity in the cerebrospinal fluid of patients with Parkinson's disease and its relation to dementia. 243 3


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