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)

Somatostatin receptors in the rat pituitary gland were characterized by binding analysis with a radioiodinated high affinity somatostatin analogue, 125I-Tyr1[D-Trp8]somatostatin. Receptor binding of this derivative reached equilibrium at 30 min and was maintained at a plateau for at least 60 min. Two L-Trp8- labeled somatostatin analogues. 125I-Tyr1- and [125I-Tyr11]somatostatin, displayed less stable and lower specific uptake and higher nonspecific binding. In contrast to the rapid degradation of the L-Trp8 ligands during binding assay, 125I-Tyr1]D-Trp8]somatostatin retained more than 80% of its binding activity after 90 min of incubation with pituitary particles. Pituitary particles bound 125I-Tyr1]D-Tyr8]somatostatin with high affinity (Ka = 8.6 +/- 1.2 X 10(9) M-1) and capacity of 54.4 +/- 2.6 fmol/mg. These binding sites showed specificity for the native peptide and its active analogues, and other peptide hormones, including angiotensin II, thyrotropin-releasing hormone, vasopressin, oxytocin, substance P, and gonadotropin-releasing hormone, did not inhibit tracer binding. A good correlation was observed between the binding affinities of several somatostatin analogues and their potencies as inhibitors of growth hormone release in rat pituitary cells. These findings emphasize the physiological importance of the pituitary somatostatin receptor in mediating the inhibitory action of the peptide on growth hormone release. The use of Tyr1[d-Trp8]somatostatin as a labeled ligand permits accurate determinations of the binding affinity and concentration of receptors for somatostatin in the normal pituitary gland and provides a basis for further studies of somatostatin receptor regulation and receptor-mediated cellular effects of the tetradecapeptide.
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PMID:Pituitary somatostatin receptors. Characterization by binding with a nondegradable peptide analogue. 612 Jan 62

In embryos of the domestic mallard, domestic fowl, and Japanese quail vasotocin-, mesotocin-, luliberin (LHRH)-, met-enkephalin-, corticotropin-, and somatostatin-immunoreactive perikarya and fiber formations were visualized at different incubation stages by means of the PAP technique (Sternberger 1979). The most striking results were: (1) Vasotocin-, mesotocin-, and luliberin-immunoreactive systems display, up to the late embryonic period, morphological features most probably related to a neurohormonal function. (2) Met-enkephalin immunoreactivity appears very late during embryonic life; it is restricted to fiber networks and not found in perikarya. (3) Corticotropin immunoreactivity is observed in the tuberal region temporarily at the end of the second and the beginning of the last third of the incubation period. (4) Somatostatin-immunoreactive material is present (i) at the end of the first third of incubation, in association with the olfactory system; (ii) during the same period, adjacent to thin-layered portions of the roof of the brain; (iii) shortly thereafter, in cells of both pancreatic primordia and thyroid gland; and (iv) onward from the middle of the incubation period, in a mesencephalic cell group. The striking difference, in the early embryo, between the mature somatostatin plays a role in the development of the brain, as well as the pancreas, and the thyroid gland.
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PMID:Immunoreactive neuropeptide systems in avian embryos (domestic mallard, domestic fowl, Japanese quail). 612 29

[125I]Iodo-Tyr1-somatostatin (SRIF) binds with high affinity to one class of sites in the rat anterior pituitary with a KD of 0.91 +/- 0.22 nM and a receptor concentration of 104.4 +/- 1.9 fmol/mg protein. This binding is saturable with respect to tissue concentration and is time-, temperature-, pH-, and calcium-dependent. It is also reversible as a function of time. The rates of association and dissociation were calculated to be 5.98 X 10(7) M-1 min-1 and 0.578 min-1, respectively. Binding of [125I]iodo-Tyr1-SRIF is not inhibited by morphine, beta-endorphin, [D-Ala2]Met-enkephalin, LHRH, TRH, histidylproline diketopiperazine, neurotensin, substance P, bombesin or vasoactive intestinal peptide. In contrast SRIF, [Tyr1]SRIF, and [D-Trp8,D-Cys14]SRIF displace [125I]iodo-Tyr1-SRIF binding with Ki values 0.10 +/- 0.05, 0.46 +/- 0.18, 0.05 +/- 0.01 nM, respectively. The constants of inhibition of a series of alanine monosubstituted analogs of SRIF are correlated (r = 0.89) with their biological potency on GH secretion. Furthermore, postnatal development patterns of [125I]iodo-Tyr1-SRIF binding sites follow the ability of SRIF to inhibit GH release. Thus, [125I]iodo-Tyr1-SRIF binding to adenohypophyseal membranes seems to reflect interaction with SRIF receptors on adenohypophyseal cells. Since biological effects of the peptide have been reported on GH, thyrotropin-stimulating hormone, and PRL secretion, further studies are required to determine the cell types upon which this binding occurs.
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PMID:Somatostatin receptors on rat anterior pituitary membranes. 612 57

Presynaptic receptors in peptidergic neurons within the brain should be considered as an important target upon which different neurotransmitters or neuromodulators can act to affect peptide release. Evidence reviewed in this paper indicates that the median eminence (ME) of the hypothalamus is an area where many such interactions at the presynaptic level take place. Release of LHRH, somatostatin and vasopressin is affected by a variety of neurotransmitters or neuromodulators, such as norepinephrine, dopamine, epinephrine, histamine, cholinergic and opioid agonists, and peptides such as angiotensin II. The actions of these agents were prevented by the use of specific receptor blockers, indicating the specificity of the response evoked. Furthermore, with the use of classical pharmacological approaches, the type and affinity of the receptor involved is well defined. Other agents, such as prostaglandins (PGE2) or steroids (estradiol) were found to affect the activity of the peptidergic neuron at the synaptic terminal by stimulating directly peptide release (as seems to be the case for the PGE2/LHRH interaction) or by changing the sensitivity of the terminal to other transmitters, as shown for estradiol. In conclusion, the evidence presented indicates that the ME is an excellent model to study presynaptic regulation of neural peptide release. A set of criteria was defined within the text to establish the physiological significance of the in vitro studies. Several of the substances tested, and particularly norepinephrine and dopamine, seem to meet all the requirements to be considered physiological presynaptic regulators of neural peptide release at the level of the ME.
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PMID:The median eminence as a model to study presynaptic regulation of neural peptide release. 612 64

The LH and FSH responses to 100 micrograms LHRH in a combined pituitary stimulation test were compared to five normal men during infusions of somatostatin-28 (SS-28) and somatostatin (SS-14) and during control infusions of haemacel. SS-28 and SS-14 were administered in equimolar concentrations of 1.8 nmol/kg body weight over 210 min and LHRH was injected as a bolus at 120 min after commencement of the infusion. SS-28 significantly reduced both LH and FSH responses to LHRH compared with control infusions. SS-14 did not significantly alter the FSH response but caused a significant reduction in the LH concentration 75 and 90 min after LHRH injection. These findings demonstrate that SS-28 has distinct biological activity in addition to its role as a putative precursor of SS-14. Inhibition of gonadotropin hormone secretion by SS-14 and SS-28 suggest that these hypothalamic peptides may play a part in the regulation of LH and FSH secretion.
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PMID:Somatostatin-28 inhibits LHRH-stimulated gonadotrophin secretion in man. 612 78

The topography and ultrastructure of LHRH and somatostatin nerve fibers in the median eminence in male rats were investigated with special reference to the relation between the fiber terminals and the perivascular space of the portal capillaries. Vibratome sections taken from the rostral and preinfundibular portions of the median eminence were immunostained with anti-LHRH or anti-somatostatin serum before plastic embedding for electron microscopy. In the external layer of the median eminence, the LHRH fibers did not directly contact the perivascular space, although they were in close proximity to the external surface of the median eminence. On the contrary, somatostatin fibers divided into branches in the external layer of the median eminence and terminated in direct contact with the perivascular space in the median eminence. LHRH fiber terminals contain immunoreactive granules, whereas somatostatin fibers are characterized by the presence of synaptic vesicle-like structures, vesicle ghosts and immunoreactive granules in their terminals. These topographical and ultrastructural differences might be regarded as a morphological manifestation of different mechanisms in the release of neurohormones.
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PMID:Topography and ultrastructure of LHRH- and somatostatin-containing axonal terminals in the median eminence of rats. 613 62

The onset of the synthesis of the releasing and inhibiting hormones, associated with their identified primary structures (LHRH, somatostatin), has been studied successfully in some vertebrates. It is known from radioimmunoassay and immunohistological studies that the synthesis of LHRH, TRH and somatostatin begins in the brain of different mammalian species (rat, mouse, guinea pig, man) during embryonic life. Much less is known about this phenomenon in birds. According to very scarce immunohistological data, the first traces of identifiable LHRH appear in the brain of the chicken on day 5 1/2 of embryonic life, while somatostatin appears on the 12th embryonic day. It is remarkable, both in mammals and birds, that the onset of trophic hormone secretion usually proceeds that of the releasing and inhibiting hormones. This would indicate that the releasing and inhibiting hormones do not play a significant role in the embryonic differentiation and induction of hormone secretion of the fetal adenohypophysis.
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PMID:Emergence of production of the brain peptides. 613 53

The coordinated activities of several networks of peptidergic neurons contribute to the overall neural regulation of reproduction and associated behaviours. Key elements are rostral hypothalamic cells that synthesize and release LHRH from their median eminence nerve terminals, subject to modulation by a variety of endogenous transmitters and neuropeptides including VIP, CCK, opioids and somatostatin. In the CNS, LHRH may also participate in intercellular communication to facilitate the expression of estrogen-sensitive sexual behavior. Vasopressin and oxytocin also appear to modulate maternal and reproductive behavior. In addition, 'oxytocinergic' neurons recorded during lactation and milk ejection display unique bursting activity patterns deemed important for efficient release of hormone. However, endogenous opioid peptides appear able to dissociate this stimulus-secretion coupling mechanism, possibly through interference with a calcium sensitive component in nerve terminals.
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PMID:CNS regulation of reproduction: peptidergic mechanisms. 614 74

In the rat, hypoglycaemia inhibits growth hormone secretion, but the mechanism is unclear. To investigate this further, we have studied the effects of glucose and 2-deoxy-D-glucose on somatostatin and LHRH release from rat hypothalamic fragments incubated in vitro. Glucose (1.35-22 mM) was added to glucose-free medium and 5 and 50 mM 2-deoxy-D-glucose were added to medium containing 5.5 mM glucose. Medium somatostatin and LHRH levels were measured by RIA. Somatostatin and LHRH released diluted in parallel with synthetic somatostatin and LHRH. Sephadex gel filtration demonstrated two molecular forms of somatostatin, 70% coeluting with somatostatin-14 and 30% with somatostatin-28; LHRH coeluted with synthetic LHRH. KCl (30-100 mM) resulted in release of somatostatin and LHRH; this was reduced in calcium-free medium. Basal and K+-stimulated somatostatin release were significantly increased by reducing glucose levels (r = -0.6, p less than 0.001). Basal LHRH was not influenced by glucose. Basal and K+-induced somatostatin release were significantly increased by 2-deoxy-D-glucose (p less than 0.05), while LHRH levels remained unchanged. Our results demonstrate that basal and K+-induced somatostatin release from rat hypothalamic fragments are modulated by local glucose concentrations, and this effect is specific as it is not paralleled by LHRH changes. We suggest that the reduction in growth hormone secretion during hypoglycaemia in the rat might be mediated, at least in part, via a direct effect of glucose on somatostatin release.
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PMID:Glucose modulation of somatostatin and LHRH release from rat hypothalamic fragments in vitro. 614 38

A superfusion method consisting of fully recovered, dissociated pituitary cells adhering to Cytodex beads has proved useful in monitoring the dynamics of hormone secretion over time. Male rat anterior pituitaries were dissociated with collagenase and Viokase, then cultured in the presence of Cytodex beads for 3-5 days, during which time the cells attached firmly to the surface of the beads. The bead-attached cells were stable and could be transferred to any vessel without the need for centrifugation or further trypsinization. For this application, the bead-attached cells were packed in a column and superfused with a low bicarbonate buffer requiring no CO2 gassing. Viability was more than 95% after 48 h in the column. The cells responded in a normal physiological manner to hypothalamic releasing and inhibitory peptides. The ED50 was 0.3 nM for somatostatin and 1.2 nM for gonadotropin-releasing hormone. A postinhibitory rebound of GH secretion was observed after the discontinuation of large doses of somatostatin. LH secretion reached maximal levels within 6 min after 10 nM gonadotropin-releasing hormone, but started declining after 2 h of continuous stimulation and dropped close to baseline within 18 h. GH release was significantly increased by prostaglandin E2, 3-isobutyl-1-methylxanthine, and 8-bromo-cAMP. LH secretion increased 5-fold in response to 1 mM 8-bromo-cAMP, but showed little increase during prostaglandin E2 or 3-isobutyl-1-methylxanthine stimulation. The cocarcinogen phorbol myristate acetate (12-O-tetradecanoyl-phorbol-13-acetate) induced secretion of all pituitary hormones and continued to do so for hours after a short pulse. The superfusion system is simple to operate and has proven effective in studying transient phenomena, desensitization, and short term kinetics of secretagogues.
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PMID:Superfusion of rat anterior pituitary cells attached to Cytodex beads: validation of a technique. 615 98


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