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)

We have previously reported that intracameral (I.C.) administration of neurotensin (NT) potently induces a time- and dose-dependent miosis in rabbits. This study was designed to determine structure-function relationships for NT-induced miosis. NT and twelve different fragments and analogs of NT, and the structurally-unrelated peptides beta-endorphin (beta-end), somatostatin (SRIF) and thyrotropin-releasing hormone (TRH) were tested in a dose equimolar to 30 micrograms of NT for their effects on pupillary diameter (PD) in rabbits. In confirmation of previous findings, NT produced significant miosis. Followed in order of duration of effect were D-Trp11-NT, D-Tyr11-NT, the N-terminal fragment NT1-12, [Gln4] - NT and NMe-NT. The N-terminal fragment NT1-8, D-Arg8-NT, and D-Phe11-NT were weakly active. In addition, the initial N-terminal fragment NT1-6 and the C-terminal fragments NT8-13 and NT9-13 did not affect PD. D-Pro10-NT, beta-end, SRIF, and TRH were totally ineffective. The results of this investigation contribute to support a role for NT on regulation of pupillary function, and suggest that the midportion of NT appears to be critical for the expression of NT-induced miosis.
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PMID:Pupillary effects of neurotensin: structure-activity relationships. 286 86

Somatostatin inhibits growth hormone (GH) and thyrotropin (TSH) secretion in the rat. Previous studies have shown that small discrete lesions of the periventricular hypothalamic (PV) and medial-basal amygdaloid (AMG) nuclei, which contain high concentrations of somatostatin neurons, reduce somatostatin-like immunoreactivity (SLI) in the median eminence (ME) by approximately two thirds and one third, respectively. The present study assessed the function of the PV and AMG somatostatin systems in the regulation of basal episodic GH and TSH secretion. Three experiments were performed in freely behaving, chronically cannulated adult male rats. In experiment 1, bilateral electrolytic lesions (20 mC) were placed in the PV at the level of the paraventricular nucleus. In experiment 2, bilateral thermal lesions (55 degrees C X 1 min) were placed in the AMG. In experiment 3, thermal lesions were placed in both the PV and AMG (PV/AMG). Blood samples were removed from animals every 15 min for 5.5 h 14-21 days postoperatively. The ME was microdissected for determination of SLI content. PV, AMG and PV/AMG lesions reduced ME SLI by 59, 26, and 91%, respectively. PV or AMG lesions had no effect on the amplitude or frequency of GH secretory peaks, GH trough levels or the total amount of GH secreted, whereas combined PV/AMG lesions reduced GH peak levels. Lesions of the AMG caused a 34% increase in mean plasma TSH levels, while PV or PV/AMG lesions reduced TSH. The latter effect was probably caused by damage to thyrotropin-releasing hormone neurons and/or axons, which are also located in the PV region. These results suggest that PV and AMG somatostatin systems may not have a significant role in the regulation of basal episodic GH secretion and the putative AMG somatostatin system exerts a significant inhibitory influence on TSH secretion.
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PMID:Regulation of growth hormone and thyrotropin secretion by somatostatin systems in rat brain. 286 24

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

The effects of somatostatin (SOM) and cholecystokinin octapeptide (CCK-8) on basal and potassium-induced release of acetylcholine (ACh) were investigated in slices of rat caudate nucleus (CN) and, for comparison, cerebral cortex (CX). Potassium (5-55 mM) produced a concentration-dependent increase in the release of [3H]ACh in the presence of extracellular Ca2+. SOM (1 microM), CCK-8 (1 microM) and the dopamine (DA) receptor agonist, apomorphine (APO, 30 microM) inhibited the K+-induced (35 mM) release of [3H]ACh by 26-32% from CN, but did not affect ACh release from CX. Other peptides (1 microM), such as Met-enkephalin, vasoactive intestinal peptide, thyrotropin-releasing hormone and substance P, had no effect on release of [3H]ACh in CN or CX. Sulpiride (SULP), a dopamine receptor antagonist, prevented the effects of APO and SOM, but not CCK-8, to inhibit [3H]ACh release. The results indicate that: (1) SOM and CCK-8 inhibit the release of [3H]ACh in CN, but not CX; and (2) the inhibitory effect of SOM, but not CCK-8, on [3H]ACh release is mediated by dopaminergic mechanisms.
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PMID:Somatostatin and cholecystokinin octapeptide differentially modulate the release of [3H]acetylcholine from caudate nucleus but not cerebral cortex: role of dopamine receptor activation. 287 39

The pituitaries of transgenic mice that express a metallothionein-somatostatin fusion gene contain high concentrations of somatostatin-14 exclusively in the gonadotrophic cells. The purpose of this study was to determine whether somatostatin expressed from the foreign fusion gene enters the normal secretory pathway within these cells. Immuno-gold labeling of serial thin sections localized somatostatin to the secretory granules of gonadotropin-producing cells. The gonadotroph-specific hypophysiotropic factor, luteinizing hormone-releasing hormone caused a dose-dependent secretion of somatostatin when applied to primary pituitary cultures from these mice. Growth hormone-releasing hormone, thyrotropin-releasing hormone, corticotropin releasing factor, and dopamine did not affect somatostatin secretion. These experiments demonstrate that a neurosecretory peptide encoded by a foreign gene can enter the regulated secretory pathway of pituitary cells from transgenic mice.
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PMID:Somatostatin is targeted to the regulated secretory pathway of gonadotrophs in transgenic mice expressing a metallothionein-somatostatin gene. 287 85

The effects of synthetic somatostatin (SRIF) on serum growth hormone (GH) concentrations stimulated by exogenous administration of synthetic thyrotropin-releasing hormone (TRH) and/or human pancreatic GH-releasing factor (hpGRF) were investigated in 4-week-old cockerels. In addition, the additive effects of TRH and hpGRF on serum GH were examined. TRH and hpGRF, when given in combination intravenously, produced an additive effect on serum GH concentration that peaked 10 min after the injection. The somatostatin did not significantly affect basal GH concentrations when given alone, but did significantly decrease the magnitude of the GH response to hpGRF. In contrast, SRIF did not significantly decrease the stimulatory effects of TRH on GH release. These results suggest that TRH and hpGRF are potent GH releasers in vivo and that their stimulating effects on GH release are additive, suggesting different mechanisms for their stimulation. The results obtained from the combination studies suggest that the main site of the stimulatory action of hpGRF is at the pituitary, and that SRIF significantly inhibited the rise in serum GH induced by a synthetic hpGRF, but not that induced by TRH.
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PMID:Interaction of human pancreatic growth hormone-releasing factor, thyrotropin-releasing hormone, and somatostatin on growth hormone release in chickens. 287 90

The effect of somatostatin (0.05 and 1.5 micrograms/kg/hr) and of thyrotropin-releasing hormone (0.1 and 1.0 microgram/kg/hr) on cholecystokinin-induced gallbladder emptying was studied in healthy volunteers by means of real-time ultrasonography. In addition, the action of increasing doses (0.05, 0.15, 0.45, and 1.35 micrograms/kg/hr) of somatostatin on resting gallbladder volume was also evaluated. Somatostatin, at the dose of 0.05 microgram/kg/hr (shown to produce blood levels similar to those measured after a meal) significantly inhibited the gallbladder contraction in response to cholecystokinin. Kinetic analysis showed that the interaction of somatostatin and cholecystokinin is of the noncompetitive type. The higher dose of the peptide (1.5 microgram/kg/hr) completely suppressed cholecystokinin-induced gallbladder contraction. In experiments carried out using somatostatin alone, a progressive increase in gallbladder volume in response to increasing doses of peptide was observed. The administration of either dose of thyrotropin-releasing hormone did not affect gallbladder emptying in any of the subjects studied. It is concluded that somatostatin is a potent inhibitor of cholecystokinin action on the gallbladder. The clear effectiveness of a very low, presumably physiological, dose indicates that somatostatin may play a physiological role in the regulation of gallbladder motor activity and provides further evidence that the peptide may act as a true hormone in man. Thyrotropin-releasing hormone does not seem to affect gallbladder motility, at least under the experimental conditions of the present study.
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PMID:Effect of somatostatin and thyrotropin-releasing hormone on cholecystokinin-induced gallbladder emptying. 287 16

The anteroventral periventricular nucleus (AVPv), which lies in the periventricular zone of the preoptic region, is critical for normal phasic gonadotropin secretion since lesions of this nucleus abolish the progesterone-induced surge of luteinizing hormone secretion from the anterior pituitary, block ovulation, and induce persistent vaginal estrus in female rats. However, very little is known about the neurotransmitter-specific pathways associated with this nucleus. In the present study we evaluated the distribution of biochemically specific cells and fibers within the AVPv and adjacent regions by using an indirect immunohistochemical method with antisera to serotonin (5-HT), dopamine beta-hydroxylase (DBH), tyrosine hydroxylase (TH), neuropeptide Y (NPY), cholecystokinin-8 (CCK), vasoactive intestinal polypeptide (VIP), substance P (SP), neurotensin (NT), corticotropin-releasing factor (CRF), luteotropin-releasing hormone (LRH), somatostatin (SS), thyrotropin-releasing hormone (TRH), oxytocin (OXY), vasopressin (VAS), adrenocorticotropic hormone (ACTH1-24), alpha-melanocyte-stimulating hormone (alpha-MSH), leucine-enkephalin (L-ENK), and calcitonin gene-related peptide (CGRP). Our findings indicate that both cells and fibers containing these putative neurotransmitters are differentially distributed in and around the AVPv in accordance with the cytoarchitectonic organization of this part of the preoptic region. The AVPv itself appears to receive strong inputs from SP-, VAS-, CCK-, and SS-containing pathways, whereas the highest densities of L-ENK-, NT-, 5-HT-, NPY-, and DBH-immunoreactive fibers were found in the cell-sparse zone just lateral to the AVPv. The suprachiasmatic preoptic nucleus (PSCh), a small group of cells located ventral to the AVPv just dorsal to the optic chiasm, contained high densities of alpha-MSH- and ACTH-immunoreactive fibers, as well as substantial numbers of fibers containing catecholamines or NPY. In contrast, a dense plexus of VAS-stained fibers was distributed fairly evenly throughout the AVPv and PSCh. Numerous L-ENK-immunoreactive cell bodies, and moderate numbers of CCK-, NT-, and CRF-stained cell bodies were found in the AVPv. The PSCh contained many TH-stained cells (presumably dopaminergic), in addition to a moderate number of CCK-containing cell bodies, while a high density of NT- and CRF-stained cells were found in the cell-sparse zone lateral to the AVPv, in addition to several CCK-, SP-, VIP-, and TH-containing cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The distribution of neurotransmitter-specific cells and fibers in the anteroventral periventricular nucleus: implications for the control of gonadotropin secretion in the rat. 288 Jun 34

Previous studies have shown that intracisternal (i.c.), but not intravenous administration of thyrotropin-releasing hormone (TRH), an endogenous tripeptide (pGlu-His-Pro-NH2), produces a time-, dose-dependent and vagus-mediated stimulation of acid secretion in rats. This study was designed to test the hypothesis that endogenous brain TRH plays a role in regulation of acid secretion in the pylorus-ligation model. In confirmation of previous reports, i.c. TRH (1 microgram) significantly (P less than 0.01) stimulated gastric acid output, gastric secretory volume and decreased gastric intraluminal pH. Intracerebroventricular (i.c.v.) infusion of TRH antiserum (anti-TRH) 30 min prior to pyloric occlusion significantly reduced acid output, secretory volume and raised gastric pH. This inhibitory gastric acid secretory response to i.c.v. anti-TRH appears to be specific since i.c.v. infusion of normal rabbit serum or antisera raised against neurotensin (NT), Leu-enkephalin (L-enk), gonadotropin-releasing hormone (GnRH), somatostatin (SRIF) and alpha-melanocyte stimulating hormone (alpha-MSH) were without measurable effect. The findings of this study indicate that endogenous brain TRH, but not NT, L-enk, GnRH, SRIF or alpha-MSH plays a physiological role in regulation of acid secretion.
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PMID:Inhibition of gastric acid secretion by immunoneutralization of endogenous brain thyrotropin-releasing hormone. 288 Jun 45

We have developed a model for combined morphological and functional in vitro studies of the isolated mediobasal hypothalamus (MBH) by considering two prerequisites: (1) the tissue must be well preserved, free of morphological artefacts and functionally unimpaired until the end of the in vitro incubation, and (2) the tissue must be processed for morphology in optimal conditions. To test our model we have studied some aspects of the luteinizing hormone-releasing hormone (LHRH) system in 4-month-old male Sprague-Dawley rats. After decapitation the MBH was isolated and put in a flask containing 0.5 ml Hepes-buffered Locke's medium gassed by 5 ml/min of O2/CO2 (95%/5%) and shaken in a water bath at 37 degrees C. After a 10-min washing, the medium was changed twice at an interval of 20 min. After the in vitro incubation the tissue was satisfactorily preserved as judged by light- and electron-microscopic analysis. LHRH, somatostatin and thyrotropin-releasing hormone could be demonstrated by alkaline phosphatase or peroxidase-antiperoxidase immunohistochemistry on semithin sections and by immunogold technique on thin sections. The LHRH secretion was close to basal values after 30 min of incubation (22.1 +/- 4.8 pg/MBH) and then remained constant for another period of 20 min (17.6 +/- 2.6 pg/MBH). During the second 20 min of incubation LHRH secretion increased in presence of 61.6 mM K+ (110.7 +/- 8.7 pg/MBH). Thus the isolated hypothalamus was excitable until the end of the in vitro incubation. We conclude that this model can be successfully used for combined morphological and functional studies.
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PMID:A model for combined morphological and functional investigations on the isolated mediobasal rat hypothalamus. 288 98


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