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 an attempt to characterize GH and PRL secretion in acromegaly, the effects of various stimuli on GH and PRL release by cultured pituitary adenoma cells derived from acromegalic patients were studied. In addition, the PRL responses of somatotroph adenoma cells were compared to those of prolactinoma cells. GH-releasing hormone-(1-44) (GHRH) consistently stimulated GH secretion in all 14 somatotroph adenomas studied in a dose-dependent manner. The sensitivity as well as the magnitude of the GH responses to GHRH were highly variable in individual tissues. Somatotroph adenomas that did not respond to dopamine were more sensitive and had greater GH responses to GHRH. In 8 of 9 somatotroph adenomas that concomitantly secreted PRL, the addition of GHRH likewise increased PRL release. Omission of extracellular Ca2+ blocked the stimulatory effect of GHRH on GH and PRL secretion. When cells were coincubated with 0.1 nM somatostatin, GH and PRL secretion induced by 10 nM GHRH were completely blocked in most adenomas. Similarly, coincubation of dopamine resulted in inhibition of GHRH-induced hormone secretion in some adenomas. Addition of TRH to the incubation medium, on the other hand, significantly stimulated GH secretion in 8 of 14 adenomas, while TRH stimulated PRL release in all of the adenomas. Vasoactive intestinal peptide (VIP) and corticotropin-releasing hormone (CRH) produced an increase in GH and PRL secretion in other adenomas. In prolactinoma cells, somatostatin and dopamine unequivocally suppressed PRL secretion; however, other stimuli including GHRH, VIP, and CRF were ineffective. TRH induced a significant increase in PRL secretion in only one prolactinoma. These results suggest that responsiveness to GHRH and somatostatin is preserved in somatotroph adenomas; the responsiveness to GHRH is inversely correlated to that to dopamine; and PRL cells associated with somatotroph adenomas possess characteristics similar to those of GH cells. Further, the GH stimulatory actions of TRH and VIP are different.
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PMID:Effects of hypophysiotropic factors on growth hormone and prolactin secretion from somatotroph adenomas in culture. 285 94

Comparison at the ultrastructural level of nerve endings containing 6 different peptides (LH-RH, C terminal ACTH, somatostatin, enkephalin, CRF, hp GRF) using immunocytochemical means has been performed. The results show that the granules are in each case very similar in size and appearance. This aspect can therefore be used to individualize the neuropeptide terminals but it does not permit to determine the nature of the peptide. In the central nervous system many different neuropeptide terminals have been observed at the ultrastructural level but in the majority of cases neither the role nor the pericarya of origin could be precised. On the contrary for the enkephalin containing nerve endings observed in the lateral septum it has been possible to prove that pericarya of origin were located in the hypothalamus and more precisely in the magnocellular dorsal nucleus.
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PMID:[The ultrastructural level of different peptidergic nerve endings in the median eminence, dorsal hypothalamus and septum]. 286 34

Neuropeptides represent a new class of compounds with important implications for the understanding of the mechanisms and treatment of epileptic disorders. Several systems of peptide modulators--in particular the opioid-like peptides, vasopressin, somatostatin, thyrotropin-releasing hormone (TRH) and ACTH--have partially demonstrated endogenous roles in some forms of epilepsy. Seizures and stressful situations may release endogenous opioid peptides and mediate postictal depression and postictal seizure refractoriness. Vasopressin is believed to increase susceptibility to convulsions and may be involved in the pathogenesis of febrile convulsions. Derangements in TRH regulation may lower thresholds for seizure expression by regulating arousal systems; however, some TRH analogs have proven to be effective anticonvulsants. Long-term alterations in somatostatin regulation could be components of focal epilepsies. ACTH is particularly useful in the treatment of infantile spasms. Pharmacological effects of these and other peptides have potentials for defining new classes of anticonvulsants. Cholecystokinin (CCK) and its analogs, the opioid peptides beta-endorphin and FK33824, TRH analogs, and several dipeptides exhibit potent anticonvulsant properties in chemical, electroshock, and genetic model screens. Convulsant actions of CRF, somatostatin, TRH, vasopressin, and high doses of endorphin or enkephalins may provide new tools to study regulatory mechanisms of cerebral excitability. The enkephalin epileptogenic effect is being developed as a predictive tool for new anti-petit mal anticonvulsants. Advances in molecular biology have identified the genes of particular peptide families. A concept has developed that the large propeptide precursors, coded by these genes, whose processing leads to functional peptide formation and release, regulate peptidergic humoral responses to external stimuli. This idea may have particular application in the understanding of the genetic basis of some seizure states. Techniques for amplification of mRNA expression have identified specific neuronal proteins and peptides. Knowledge of protein and propeptide structural cleavage sites has suggested previously unknown candidates for modular systems in epileptic states. Technological advances in automated peptide sequencing and synthesis have allowed the development of metabolically resistant analogs and antagonist peptides. The anticonvulsant potencies of CCK, TRH, and opioid peptides have been defined more clearly with these methods.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neuropeptides: anticonvulsant and convulsant mechanisms in epileptic model systems and in humans. 287 23

A new synthetic biotinylated N-terminal analog of CRF was used to study its binding, endocytosis, and route of processing. The new analog was fully bioactive compared to rat(r) CRF in an ACTH bioassay and pituitary membrane receptor assay. In 1- to 4-day cultured pituitary cell monolayers, CRF receptors were labeled for 1-biotinylated rCRF (1-bio-CRF) and demonstrated with avidin-fluorescein (Ar-Fl) in living cells or with avidin-biotin-peroxidase complex (ABC) in fixed cells. The percentages of fluorescein-labeled cells were comparable to those stained with the ABC technique. The specificity of binding by 1-bio-CRF was shown by the ability of unlabeled CRF to inhibit staining, whereas 100 nM arginine vasopressin, angiotensin II, or somatostatin was without effect. Treatment of the cells with 100 nM glucocorticoids for 1 or 24 h before the 3-min stimulation with 1-bio-CRF caused a 50-60% reduction in the percentage of cells stained with either ABC or Av-Fl. Pretreatment with vehicle, a lower dose of corticosterone (10 nM), or other steroids (dihydrotestosterone or epitestosterone) did not decrease the percentage of cells stained with the ABC technique. The lower dose of glucocorticoids decreased the stain with Av-Fl by 50% after 1 h of pretreatment. Electron microscopic analysis of binding and endocytosis of 1-bio-CRF stained with the ABC technique showed patches of stain on coated pits and microvilli during the first 3 min of exposure. Internalization in vesicles and receptosomes was also seen during the first 3 min. Some stain was found on secretion granules as early as 1 min after exposure. Five minutes after exposure, the stain was in receptosomes, Golgi cisternae, condensing vesicles in the transreticular Golgi region, and 23% of the granules in the cytoplasm. During the later exposure periods (15-30 min), stain was also seen in multivesicular bodies. The correlative light and electron microscopic studies showed that 1-bio-CRF is rapidly internalized after patching on the surface and is ultimately found in multivesicular bodies or granules. We postulate that these structures are involved in processing or degradation of the ligand.
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PMID:Cytochemical studies of corticotropin-releasing factor (CRF) receptors in anterior lobe corticotropes: binding, glucocorticoid regulation, and endocytosis of [biotinyl-Ser1]CRF. 287 85

Certain neuropeptides previously linked to stress and implicated in CNS control of analgesia/algesia were tested using a recently developed analgesiometric model, the rabbit ear-withdrawal test. The latency to ear withdrawal increased in a dose-related manner after beta-endorphin was injected intracerebroventricularly (IVC). Intermediate doses (0.5 and 1.0 micrograms) of adrenocorticotropic hormone (ACTH) caused hyperalgesia as indicated by decreases in latency. Corticotropin-releasing factor (CRF, 0.5 and 1.0 micrograms) also caused significant hyperalgesia late in the testing period. alpha-Melanocyte stimulating hormone (alpha-MSH, 0.25-2.0 micrograms), a molecule that shares the first 13 amino acid sequence with ACTH, and somatostatin (0.25-2.0 micrograms), caused no significant change in latency. However, 1.0 microgram doses of each peptide antagonized the analgesic effect of beta-endorphin (1.0 microgram) in the following order of potency: ACTH = alpha-MSH greater than CRF greater than somatostatin. The results support the idea that CNS peptides that are released during stress can exert opposing actions on acute pain, even though they may cause little effect alone.
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PMID:Influence of centrally administered peptides on ear withdrawal from heat in the rabbit. 288 94

Primary cultures of rat hypothalamic neurones were maintained either in a serum-supplemented medium or in a serum-free chemically defined medium for up to 6 weeks. The release of the 41 amino acid-containing peptide, corticotrophin-releasing factor (CRF-41), vasopressin (AVP) and somatostatin (SRIF) were followed using immunoassays. In response to K+ (56 mmol/l) depolarization both the quantities of peptides released and the magnitude of responses were significantly greater from cultures maintained in the fully supplemented defined medium. As a consequence, release of CRF-41 and AVP could be measured directly, without requiring the concentration step necessary for cultures grown in serum. The response to K+ depolarization increased with the age of the culture, suggesting neuronal maturation. Responses to K+ depolarization were Ca2+-dependent, and the addition of corticosterone (100 nmol/l) to the defined medium caused a significant reduction in the response of neurones secreting CRF-41 and AVP, but not those secreting SRIF, to depolarization. This suggests the retention in vitro of the responsiveness of stress-associated neuropeptides to the negative feedback effects of corticosterone. Neurones producing CRF-41 and AVP responded significantly in a dose-dependent manner to acetylcholine stimulation, whereas those producing SRIF did not. As cultures matured, the CRF-41- and AVP-producing neurones became more sensitive to acetylcholine with the maximal response at 1 nmol acetylcholine/l. In conclusion, the culture of rat hypothalamic neurones is improved in terms of peptide output when the cultures are maintained in a defined medium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of peptide release from fetal rat hypothalamic neurones cultured in defined media and serum-containing media. 289 60

Growth hormone releasing factor (GHRF) was examined to determine whether it affects somatostatin (SRIF) release from cultured rat hypothalamic cells and fragments in vitro. The hypothalami of rat fetuses were collected on the 17th day of pregnancy under a dissection microscope. Thirty hypothalami were placed in phosphate buffered saline, and the cells were dispersed with 0.1% collagenase. The dispersed cells were cultured in Dulbecco's modified Eagle medium (DMEM) containing 10% horse serum and 2.5% fetal calf serum at 37 degrees C under 5% CO2 in air. On the 12th day of culture, the cells were washed with Krebs Ringer bicarbonate buffer containing glucose (KRBG), and then incubated with KRBG for 1 hour. The medium was replaced with KRBG alone (control) or KRBG containing test substances, and incubated for another hour. SRIF released into the medium was quantitated by RIA. The mean basal release of SRIF was 14.7 +/- 0.9 pg/dish/hour. One-tenth, 1, and 10nM hpGRF44 stimulated SRIF release by 1.4, 1.5, and 1.8 fold respectively in a dose-related manner. Ten nM ovine corticotropin releasing factor (o-CRF) also stimulated SRIF release by 2.3 fold. One, 10, and 100 nM hpGRF44, 10nM o-CRF, 10nM thyrotropin releasing hormone (TRH) and 60 mM K+ also stimulated SRIF release from rat hypothalamic fragments. Removal of Ca++ from the medium resulted in a decrease of basal release of SRIF. In Ca++ free medium, 10nM hpGRF44 failed to release SRIF. One-tenth nM hpGRF44, 10nM GnRH, and 10nM VIP have no effect on SRIF release statistically. The results of this study demonstrate that a high concentration of GHRF stimulates SRIF release from the hypothalamus in vitro, suggesting a possibility that GHRF may increase the release of SRIF from the median eminence and the hypothalamus in vivo under certain conditions.
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PMID:The stimulation of somatostatin release by hpGRF44 from rat hypothalamic cells and fragments in vitro. 289 40

The laterodorsal tegmental nucleus (ntdl) contains a cluster of cells located just medial to the locus coeruleus in the pontine brainstem. The ntdl has been shown to project both rostrally to the forebrain and diencephalon and caudally to the spinal cord. In an effort to characterize this region neurochemically, the present study was conducted to identify a variety of neurochemicals localized within perikarya and fibers of the ntdl and surrounding nuclei. Rats were perfused with formalin, and brain sections were processed for fluorescence immunocytochemistry and acetylcholinesterase (AChE). Of the neurochemicals screened, atrial natriuretic factor (ANF), choline acetyltransferase (ChAT), cholecystokinin (CCK), calcitonin gene-related peptide (CGRP), dynorphin B (Dyn B), galanin, somatostatin, substance P, neurotensin (NT), neuropeptide Y (NPY), vasopressin, vasoactive intestinal polypeptide (VIP), serotonin (5HT), glutamic acid decarboxylase (GAD), and tyrosine hydroxylase (TH) were studied. AChE and ChAT staining revealed that the ntdl contains mostly cholinergic neurons. In addition, brightly reactive substance P and galanin and paler staining CRF, ANF, CGRP, NT, VIP, and Dyn B cell bodies were found within the ntdl. Varicose fibers in this nucleus also contained these peptides in addition to CCK, GAD, TH, 5HT, and NPY. The dorsal tegmental nucleus, dorsal raphe nucleus, locus coeruleus, and the parabrachial region contained a dense and varied assortment of peptides with distinct positions and patterns. This multiplicity of neurochemicals within this area suggests a possible influence on a variety of functions modulated by the ntdl and other closely associated tegmental nuclei.
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PMID:Immunocytochemical localization of peptides and other neurochemicals in the rat laterodorsal tegmental nucleus and adjacent area. 289 81

Neurotensin (NT) differentially altered ethanol-induced anesthesia as measured by duration of loss of righting response or by blood ethanol levels producing loss of righting response in mice (LS and SS) which were selectively bred for differences in response to ethanol. At doses of 5-500 ng i.c.v., NT increased ethanol sensitivity in SS mice, but not in LS mice, as measured by blood ethanol concentrations at loss of righting response. At higher doses, 0.5-10 micrograms i.c.v., NT enhanced the sensitivity of both SS and LS mice to ethanol-induced anesthesia. The hypothermic effect of ethanol determined at loss of righting response was not altered in either LS or SS mice at low doses of NT, but at higher doses NT enhanced ethanol-induced hypothermia in both lines of mice. The altered anesthetic sensitivity was specific for ethanol in that NT did not alter pentobarbital-induced sleep time in either LS or SS mice and halothane anesthesia was altered slightly only in LS mice. NT analogues, N-acetyl-NT8-13, and [D-Trp11]-NT but not NT1-8 enhanced the anesthetic action of ethanol in SS mice. Bombesin, cholecystokinin sulfate, substance P, [D-Trp8, D-Cys14]-somatostatin and corticotropin releasing hormone (CRF) were not effective in enhancing ethanol-induced anesthesia in LS or SS mice. CRF appeared to decrease ethanol sensitivity in LS but not in SS mice. Beta-Endorphin (beta-END) markedly increased the ethanol sensitivity of SS and to a lesser extent of LS mice at relatively high doses, e.g. 0.5-1.0 micrograms i.c.v. The results of the present study indicate that differences in brain sensitivity of LS and SS mice to ethanol may be mediated by genetic differences in NT systems. Likewise, NT, and probably beta-endorphin, may interact with other neurochemical processes that are involved in the mechanism of ethanol-induced anesthesia and that differ genetically in LS and SS mice.
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PMID:Neurotensin selectively alters ethanol-induced anesthesia in LS/Ibg and SS/Ibg lines of mice. 294 96

Recent reports indicate that the main effect of systemically administered angiotensin II (AII) on ACTH release is probably due to some central nervous system mechanism. The present studies were designed to investigate whether the central action of AII on ACTH release is directly mediated through CRF. In order to test the participation of endogenous CRF in the AII-induced ACTH release in vivo, intact and pharmacologically blocked (pretreated with chlorpromazine-morphine-nembutal) female rats were injected iv with AII (8 nmol/100 g BW). Plasma levels of ACTH as well as CRF content in the median eminence (ME) and medial basal hypothalamus (MBH) were evaluated before and 1, 2.5, and 5 min after treatment. These responses were compared with the effect of 1 min ether exposure on hypothalamic CRF content and plasma ACTH levels in unanesthetized animals. AII injection and ether exposure increased plasma ACTH levels several-fold at both 2.5 and 5 min post treatment in intact rats. Conversely, AII failed to induce any significant increase in plasma ACTH levels in centrally blocked rats at any interval studied. On the other hand, AII injection and ether inhalation acted in similar fashion on CRF content in ME, inducing fast depletion at 1 min post treatment, recovering to control values at 2.5 min after injection, and finally, accumulating peptide at 5 min post treatment. In addition, CRF content in the MBH decreased significantly at 5 min, under both experimental conditions; AII had no effect on hypothalamic CRF content in centrally blocked rats. In vitro experiments using whole MBH (containing ME) fragments incubated with either neural peptides or high K+ solutions indicate that AII possesses a CRF releasing effect at concentrations of 10(-6) M or more. Conversely, other hypothalamic peptides, such as LHRH, TRH, and somatostatin did not induce significant release of CRF at any of the concentrations assayed (10(-7) to 10(-5) M). On the other hand, high K+ solutions released CRF in a concentration-related manner (15-60 mM). These studies suggest that the central effect of AII stimulation on ACTH release in vivo could be, at least in part, through the release of hypothalamic CRF into the portal circulation.
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PMID:Angiotensin II and adrenocorticotropin release: mediation by endogenous corticotropin-releasing factor. 301 75


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