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 investigate the potential antagonistic actions of the two main neuroregulators of the somatotropinergic system (GRF-SS-GH-SM axis), growth hormone-releasing factor (GRF) and somatostatin (SS) at the central level, the effects of GRF and SS on locomotor activity (LA) were studied in a computerized system. Male Wistar rats (N = 6-9 per group) received i.p. or i.c.v. GRF(1-44)NH2 or SS(1-14) in doses ranging from 0.1-30 micrograms, and LA was automatically recorded in the OUCEM-86 system (Osaka University Computerized Electronic Maze) for 30-min periods. The peripheral administration of SS (1 microgram, i.p.) did not alter LA, while GRF (1 microgram, i.p.) increased LA from 20.35 +/- 4.18 to 36.25 +/- 6.98 IO/min (p less than 0.005). After central injection, SS (1 microgram; i.c.v.) decreased LA from 31.16 +/- 6.90 to 20.88 +/- 2.82 IO/min (p less than 0.005) and GRF (1 microgram, i.c.v.) increased LA to 47.60 +/- 5.35 IO/min (p less than 0.005). SS- and GRF-induced LA changes were time- and dose-dependent (SS: ED50 = 1.83 nmol, Emax = 6.10 nmol; GRF: ED50 = 99.1 pmol, Emax = 1.98 nmol). The maximum effect of GRF appeared during the first 5 min, showing activity 10-15 sec post-injection, while the lowest activity induced by SS was registered 15-30 min after injection, although a significant reduction in LA was detected 5-10 sec after i.c.v. administration. With doses higher than 10 micrograms (i.c.v.) SS provoked "barrel rotation", tremors and stereotyped behaviors. The GRF-induced hyperkinetic syndrome showed a linear pattern with doses up to 10 micrograms, and a plateau with 10-15 micrograms. Doses higher than 20 micrograms induced convulsion, uncontrolled movements and a high death rate during the following 12-24 h. In conclusion, according to the present results, GRF and SS exert antagonistic effects on LA in a time- and dose-dependent manner, the former stimulating LA, and the latter inhibiting it.
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PMID:Antagonistic effects of growth hormone-releasing factor (GRF) and somatostatin on locomotor activity: GRF-induced hyperkinetic syndrome. 198 32

To date, the effects of long-term growth hormone (GH)-releasing hormone [GHRH(1-29)-NH2] treatment on the plasma concentrations of somatostatin-like immunoreactivity (SLI) remain undefined. In the present study, the effect of GHRH(1-29)-NH2 therapy on plasma SLI levels has been studied in 11 non-GH-deficient children. The pattern of administration was 5 micrograms/kg body weight, given subcutaneously once every day. There was no significant change in plasma SLI levels after bolus injection of GHRH(1-29)-NH2 before and during GHRH(1-29)-NH2 therapy. However, plasma SLI rose in basal plasma and nocturnal sleep after 3 months of GHRH(1-29)-NH2 therapy and remained the same during 6 months of treatment with GHRH(1-29)-NH2. The reason for this finding is uncertain, but an increase in SLI release from the enteroinsular axis is a possible explanation. The association of our findings with the role of the circulating SLI on nutrient homeostasis and the effects of GNRH on growth velocity is discussed.
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PMID:Plasma somatostatin-like immunoreactivity during growth-hormone-releasing hormone therapy in non-growth-hormone-deficient children. 198 47

GH-releasing peptide (His-DTrp-Ala-Trp-DPhe-Lys-NH2 or GHRP) releases GH by a unique and complementary dual site of action on the hypothalamus and pituitary. These effects are mediated via non-GH-releasing hormone (non-GHRH) and nonopiate receptors in rats. Select types of opiates are known to release GH by a hypothalamic site of action, and thus, the dermorphin heptapeptide and benzomorphan opiate agonist 2549 used in this study presumably act on the hypothalamus to release GH. Neither dermorphin nor 2549 released GH or augmented the GH responses of GHRP or GHRH in vitro by a direct pituitary action, while GHRH antiserum inhibited the GH response of both dermorphin and 2549 in vivo. Evidence indicates that these opiates and GHRP administered together synergistically release GH, demonstrating the independent action(s) of GHRP and the opiates. Present data indicate that one of the major differences in the actions of dermorphin, 2549, and GHRP is the inhibition of somatostatin (SRIF) release by the opiates but not by GHRP. Although the actions of dermorphin, 2549, and GHRP on GH release are GHRH dependent, release of endogenous GHRH does not explain how GH is released synergistically by the combination of these peptides. It is proposed that dermorphin/2549 synergistically release GH with GHRP or GHRH because these opiates inhibit SRIF release. Since the GHRP plus GHRH synergistic GH release was not explained by inhibition of SRIF or stimulation of GHRH, an alternative mechanism is proposed to explain how GHRP synergistically release GH in combination with GHRH. The complementary, rather dramatic synergistic interaction of GHRP, GHRH, and dermorphin or GHRP, GHRH, and 2549 in releasing GH again strongly supports the independent actions of these compounds.
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PMID:On the actions of the growth hormone-releasing hexapeptide, GHRP. 200 15

Growth hormone-releasing hormone (GHRH) increases serum GH levels in a dose-dependent manner. Pyridostigmine (PD), an acetylcholinesterase inhibitor, is able to elicit GH secretion when administered alone and to enhance the GH response to GHRH in normal subjects, probably via a decrease in the hypothalamic release of somatostatin. The aim of the present study was to investigate if an enhancement of the cholinergic tone was able to influence the dose-response relationship between GHRH and GH in normal adult subjects. Six healthy adult volunteers underwent 10 experimental protocols. They were: human GHRH (1-29)NH2, 1 micrograms/kg injected as an intravenous (IV) bolus 60 minutes after (a) PD, 120 mg administered orally, or (b) placebo, two tablets administered orally; GHRH, 0.3 micrograms/kg injected as an IV bolus 60 minutes after (c) PD or (d) placebo; GHRH, 0.1 micrograms/kg injected as an IV bolus 60 minutes after (e) PD or (f) placebo; GHRH, 0.01 micrograms/kg injected as an IV bolus 60 minutes after (g) PD or (h) placebo; saline, 1 mL injected as an IV bolus 60 minutes after (i) PD or (l) placebo. The GH response in placebo-treated subjects was similar after 1 microgram/kg and 0.3 microgram/kg GHRH, while the 0.1 microgram/kg dose elicited a lower response. The 0.01 microgram/kg dose of GHRH did not significantly increase GH levels as compared with saline. After PD, the GH responses to GHRH were greatly enhanced at all doses tested: 1.0, 0.3, and 0.1 microgram/kg GHRH all elicited similar GH responses; the GH response to 0.01 microgram/kg GHRH was lower, but was still higher than that observed after saline.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of cholinergic tone in modulating the growth hormone response to growth hormone-releasing hormone in normal man. 202 38

Radioimmunoassayable IGF-I levels were measured in the cerebrospinal fluid and plasma of pig fetuses at 94 days gestational age. Mean plasma IGF-I levels were 128.5 +/- 5.8 micrograms/l while the concentration in the cerebrospinal fluid was 25.8 +/- 4.4 micrograms/l. The effect of intracerebroventricular administration of IGF-I on circulating GH levels was also studied in pig fetuses in utero. Eighteen pig fetuses were fitted with indwelling carotid artery and jugular vein catheters. Nine fetuses were given 1500 ng of pure IGF-I in 100 microliters 0.9% saline by direct injection into a right lateral ventricle. Nine further fetuses (controls) were similarly given 100 microliters of saline without IGF-I. GH levels in the control fetuses were approximately 200 micrograms/l and showed marked fluctuations with episodic intervals of about 40 min. By contrast, in the IGF-I-treated fetuses, GH levels were dramatically lowered by 20 min after IGF administration and remained low throughout the 4-h study. The episodic variations in GH were abolished and levels remained fairly constant at ca. 40 micrograms/l. From these results we surmise that the low levels of IGF-I in the fetus may contribute to their high GH levels. At this stage it is not possible to identify whether the IGF-I inhibition is a direct effect on the pituitary or is mediated by increased somatostatin, decreased GHRH or both.
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PMID:Intracerebral administration of insulin-like growth factor I decreases circulating growth hormone levels in the fetal pig. 202 15

The effect of electrical stimulation of the hypothalamic periventricular nucleus (PVN) on plasma GH profile was studied in unanesthetized female Wistar rats. A bipolar concentric electrode was implanted into the PVN, hypothalamic ventromedial nucleus (VMH), or intervening area between the PVN and VMH. Serial blood specimens were collected from an indwelling right atrial cannula. Plasma GH levels were reduced significantly during electrical stimulation of PVN, and a large rise of plasma GH levels followed after cessation of stimulation. An identical plasma GH profile was observed in response to the repeated stimulation. This rebound secretion of GH was completely inhibited by the administration of rat GRF antiserum. The effect of electrical stimulation of VMH on plasma GH levels was similar to that of PVN stimulation. However, the stimulation of hypothalamic area intervening between PVN and VMH was not followed by a surge of GH secretion. Since a continuous exposure of somatotrophs to GRF even in a concurrent presence of somatostatin (SS) is known to induce attenuation of the GH response to GRF through receptor effect, the results suggest that the release of endogenous GRF is augmented following the cessation of electrical stimulation of neurons providing hypophysiotropic SS.
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PMID:Electrical stimulation of hypothalamic periventricular nucleus is followed by a large rebound secretion of growth hormone in unanesthetized rats. 204 88

OBJECTIVE The aim of the study was to investigate whether pyridostigmine, a cholinesterase inhibitor which is thought to act at the hypothalamus to inhibit somatostatin secretion, would augment spontaneous or GHRH-stimulated serum GH levels in patients with GH-insufficiency. DESIGN Oral pyridostigmine 60 mg or placebo was administered at the start of a 9-h subcutaneous infusion of either GHRH (1-29)NH2 10 micrograms/kg/h or saline control. Studies were performed during the daytime (0900-1800 h) in five patients, and the night-time (2100-0600 h) in a further five. PATIENTS Ten short, pre-pubertal children (aged 6-11 years; eight boys) with growth hormone insufficiency were studied. MEASURES Blood for serum GH was sampled every 20 min, and analysed using the PULSAR program. RESULTS The subcutaneous infusion of GHRH 10 micrograms/kg/h increased mean serum GH levels (+/- SEM): by day 17.7(+/- 6.8) vs placebo 2.2(+/- 0.4) mU/l (P less than 0.01), and by night 26.9(+/- 3.3) vs 5.5(+/- 1.3) mU/l (P less than 0.05). There was a significant rise in mean 'baseline' GH concentration: by day 5.5(+/- 1.7) vs 1.0(+/- 0.0) mU/l (P less than 0.05); and night 8.2(+/- 2.7) vs 1.3(+/- 0.3) mU/l (P less than 0.05). Pyridostigmine failed to produce a significant overall increase in either spontaneous or GHRH-stimulated GH secretion by day or night, although there was a significant rise in mean GH levels during the 3 h following pyridostigmine administration in the morning: 4.4(+/- 1.1) vs 2.4(+/- 0.5) mU/l (P less than 0.001). GHRH or pyridostigmine given singly or in combination had no significant effect on the number of pulses. Side-effects attributable to pyridostigmine occurred in seven children. CONCLUSIONS Pyridostigmine, either on its own or as an adjuvant therapy in combination with GHRH, acts for only a brief time and does not offer any potential benefit in the management of children with short stature.
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PMID:Pyridostigmine fails to increase either spontaneous or GHRH-stimulated GH secretion during day or night in growth hormone-insufficient children. 206 Jan 50

The effect of intrathecal (i.t.) vasoactive intestinal peptide (VIP) and an analogue of growth hormone releasing factor (GRF) with putative VIP antagonistic property, (Ac-Try1, D-Phe2)-GRF-(1-29), on the nociceptive flexor reflex was studied in decerebrate, spinalized, unanesthetized rats. VIP (10 pM) facilitated the flexor reflex for several minutes. A similar facilitation was induced by the VIP antagonist applied i.t. with a potency 15 times less than that of VIP. Pre-administration of the VIP antagonist dose-dependently antagonized the reflex facilitation by i.t. VIP. In contrast, the reflex facilitation induced by i.t. substance P, somatostatin, calcitonin gene-related peptide and galanin was not influenced by the VIP-antagonist. The VIP antagonist by itself did not depress the flexor reflex over the dose range of 3 pM-3 nM and neither did it block the facilitation of the flexor reflex induced by a brief conditioning electrical stimulus train that activated the C-afferents in skin innervated by the sural nerve. The present results indicate that this GRF analogue is an effective and specific VIP antagonist in the rat spinal cord. Furthermore, it is suggested that VIP may not be involved in the transmission of cutaneous nociceptive information under normal conditions.
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PMID:An analogue of growth hormone releasing factor (GRF), (Ac-Try1, D-Phe2)-GRF-(1-29), specifically antagonizes the facilitation of the flexor reflex induced by intrathecal vasoactive intestinal peptide in rat spinal cord. 206 98

The comparative distribution of peptidergic neural systems in the brain of the euryhaline, viviparous teleost Poecilia latipinna (green molly) was examined by immunohistochemistry. Topographically distinct, but often overlapping, systems of neurons and fibres displaying immunoreactivity (ir) related to a range of neuropeptides were found in most brain areas. Neurosecretory and hypophysiotrophic hormones were localized to specific groups of neurons mostly within the preoptic and tuberal hypothalamus, giving fibre projections to the neurohypophysis, ventral telencephalon, thalamus, and brain stem. Separate vasotocin (AVT)-ir and isotocin (IST)-ir cells were located in the nucleus preopticus (nPO), but many AVT-ir nPO neurons also displayed growth hormone-releasing factor (GRF)-like-ir, and in some animals corticotrophin-releasing factor (CRF)-like-ir. The main group of CRF-ir neurons was located in the nucleus recessus anterioris, where coexistence with galanin (GAL) was observed in some cells. Enkephalin (ENK)-like-ir was occasionally present in a few IST-ir cells of the nPO and was also found in small neurons in the posterior tuberal hypothalamus and in a cluster of large cells in the dorsal midbrain tegmentum. Thyrotrophin-releasing hormone (TRH)-ir cells were found near the rostromedial tip of the nucleus recessus lateralis. Gonadotrophin-releasing hormone (GnRH)-ir cells were present in the nucleus olfactoretinalis, ventral telencephalon, preoptic area, and dorsal midbrain tegmentum. Molluscan cardioexcitatory peptide (FMRF-amide)-ir was colocalized with GnRH-ir in the ganglion cells and central projections of the nervus terminalis. Melanin-concentrating hormone (MCH)-ir neurons were restricted to the tuberal hypothalamus, mostly within the nucleus lateralis tuberis pars lateralis, and somatostatin (SRIF)-ir neurons were numerous throughout the periventricular areas of the diencephalon. A further group of SRIF-ir neurons extending from the ventral telencephalon into the dorsal telencephalon pars centralis also contained neuropeptide Y (NPY)-, peptide YY (PYY)-, and NPY flanking peptide (PSW)-like-ir. These immunoreactivities were, however, also observed in non-SRIF-ir cells and fibres, particularly in the mesencephalon. Calcitonin gene-related peptide (CGRP)-like-ir had a characteristic distribution in cells grouped in the isthmal region and fibre tracts running forward into the hypothalamus, most strikingly into the inferior lobes. Antisera to cholecystokinin (CCK) and neurokinin A (NK) or substance P (SP) stained very extensive, separate systems throughout the brain, with cells most consistently seen in the ventral telencephalon and periventricular hypothalamus. Broadly similar, but much more restricted, distributions of cells and fibres were seen with antisera to neurotensin (NT) and vasoactive intestinal peptide (VIP).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Comparative distribution of neuropeptide-immunoreactive systems in the brain of the green molly, Poecilia latipinna. 208 20

The central action of peptides to influence GI motility in experimental animals is summarized in Table 1. TRH stimulates gastric, intestinal, and colonic contractility in rats and in several experimental species. A number of peptides including calcitonin, CGRP, neurotensin, NPY, and mu opioid peptides act centrally to induce a fasted MMC pattern of intestinal motility in fed animals while GRF and substance P shorten its duration. The dorsal vagal complex is site of action for TRH-, bombesin-, and somatostatin-induced stimulation of gastric contractility, and for CCK-, oxytocin- and substance P-induced decrease in gastric contractions or intraluminal pressure. The mechanisms through which TRH, bombesin, calcitonin, neurotensin, CCK, and oxytocin alter GI motility are vagally mediated. An involvement of central peptidergic neurons in the regulation of gut motility has recently been demonstrated in Aplysia, indicating that such regulatory mechanisms are important in the phylogenesis. Alterations of the pattern of GI motor activity are associated with functional changes in transit. TRH is so far the only centrally acting peptide stimulating simultaneously gastric, intestinal, and colonic transit in various animals species. Opioid peptides acting on mu receptor subtypes in the brain exert the opposite effect and inhibit concomitantly gastric, intestinal, and colonic transit. Bombesin and CRF were found to act centrally to inhibit gastric and intestinal transit and to stimulate colonic transit in the rat. The antitransit effect of calcitonin and CGRP is limited to the stomach and small intestine. The delay in GI transit is associated with reduced GI contractility for most of the peptides except central bombesin that increases GI motility. Nothing is known about brain sites through which these peptides act to alter gastric emptying and colonic transit. Regarding brain sites influencing intestinal transit, TRH-induced stimulation of intestinal transit in the rat is localized in the lateral and medial hypothalamus and medial septum. The periaqueductal gray matter is a responsive site for mu receptor agonist- and neurotensin-induced inhibition of intestinal transit. The neural pathways from the brain to the gut whereby these peptides express their stimulatory or inhibitory effects on GI transit is vagal dependent with the exception of calcitonin. It is not known whether the vagally mediated inhibition of GI transit by these peptides results from a decrease activity of vagal preganglionic fibers synapsing with excitatory myenteric neurons or an activation of vagal preganglionic neurons synapsing with inhibitory myenteric neurons. The lack of specific antagonists for these peptides has hampered the assessment of their physiological role.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Central nervous system action of peptides to influence gastrointestinal motor function. 210 14


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