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

We propose that there exists within the avian, and perhaps more generally in the vertebrate retina, a two-state nonadapting flip-flop circuit, based on reciprocal inhibitory interactions between the photoreceptors, releasing melatonin, the dopaminergic amacrine cells, and amacrine cells which contain enkephalin-, neurotensin-, and somatostatin-like immunoreactivity (the ENSLI amacrine cells). This circuit consists of two loops, one based on the photoreceptors and dopaminergic amacrine cells, and the other on the dopaminergic and ENSLI amacrine cells. In the dark, the photoreceptors and ENSLI amacrine cells are active, with the dopaminergic amacrine cells inactive. In the light, the dopaminergic amacrine cells are active, with the photoreceptors and ENSLI amacrine cells inactive. The transition from dark to light state occurs over a narrow (< 1 log unit) range of low light intensities, and we postulate that this transition is driven by a graded, adapting pathway from photoreceptors, releasing glutamate, to ON-bipolar cells to dopaminergic amacrine cells. The properties of this pathway suggest that, once released from the reciprocal inhibitory controls of the dark state, dopamine release will show graded, adapting characteristics. Thus, we postulate that retinal function will be divided into two phases: a dopamine-independent phase at low light intensities, and a dopamine-dependent phase at higher light intensities. Dopamine-dependent functions may show two-state properties, or two-state properties on which are superimposed graded, adapting characteristics. Functions dependent upon melatonin, the enkephalins, neurotensin, and somatostatin may tend to show simpler two-state properties. We propose that the dark-light switch may have a role in a range of light-adaptive phenomena, in signalling night-day transitions to the suprachiasmatic nucleus and the pineal, and in the control of eye growth during development.
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PMID:A retinal dark-light switch: a review of the evidence. 878 68

Dopamine agonists are able to restore ovulatory cycles in 80-90% of hyperprolactinemic patients and to reduce tumoral volume (often dramatically) in 80% of macroprolactinomas. Their side-effects will be reduced with the use of parenteral forms or new agonists currently in preparation. Somatostatin analogues administered either subcutaneously by three daily injections (octreotide) or intramusculary with a long-acting formulation every 10-15 days (lanreotide) are able to "normalize" GH levels in 70% of acromegalic patients and to shrink tumor in half of the patients. Side effects are generally minor but an increased incidence of gallstones has been reported. These somatostatin analogs are also very effective in the treatment of TSH-secreting adenomas. Medical treatment of other pituitary adenomas is much more disappointing.
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PMID:[Medical treatment of pituitary adenoma]. 888 Nov 66

In cultured pituitary cells of tilapia, gonadotropin-releasing hormone (GnRH; 10 nM 4-24 h), elevation of cyclic AMP (by 10 microM forskolin or 0.2 mM 3-isobutyl-1-methylxanthine: IBMX 0.5-36 h) or activation of protein kinase C (PKC; by 12.5 nM tetradecanoyl phorbol-13-acetate: TPA, 0.5-24 h) all increased gonadotropin (GtH) II beta steady state mRNA levels by three to four-fold. The involvement of PKA and PKC in the GnRH stimulatory effect on both GtH release and GtH II beta mRNA levels was corroborated by use of the PKA and PKC inhibitors, H89 and GF109203X, respectively (100 nM) which attenuated the GnRH effect. Incubation with actinomycin D (8 microM, 4-21 h) after preexposure for 24 h to either forskolin (10 microM) or TPA (12.5 nM), revealed that rates of transcript degradation were slower in forskolin-treated cells (T 1/2 = 14.1 h) than in control or TPA-treated cells (T 1/2 = 8.47 or 8.38 h), suggesting a stabilizing effect on the mRNA. Dopamine (DA; 10 microM, 4-36 h) had no apparent effect on steady state mRNA levels of GtH II beta, but reduced GtH release by as much as 75%. Steady state levels of growth hormone (GH) mRNA were not affected by exposure to GnRH (10 nM, 4-24 h), although GH release was more than doubled. Similarly, activation of PKC (by TPA 12.5 nM, 1.5-36 h), which was shown to be essential for the GnRH-stimulatory effect on GH release, did not alter levels of the GH transcript, but increased GH release by more than fivefold. DA (10 microM, 4-24 h) moderately increased GH transcript levels (160%) with similar kinetics but lower potency than direct elevation of cAMP (by 10 microM forskolin or 0.2 mM IBMX, 0.5-36 h) which increased transcript levels by more than fourfold. The involvement of PKA in the DA effect was confirmed when the PKA inhibitor H89 (100 nM, 15 min prior to DA exposure) attenuated the DA effect on GH mRNA levels. Exposure of cells to actinomycin D (8 microM, 2-16 h) after treatment with forskolin (10 microM, 24 h) led to a slower rate of transcript degradation than in control cells (T 1/2 = 6.5 h vs. T 1/2 = 4.36 h), suggesting that cAMP also elicits a stabilizing effect on GH mRNA. Somatostatin (100 nM, 0.5-36 h) had no clear effect on GH transcript levels, but reduced GH release by as much as 90%. These results suggest that activation of either cAMP-PKA or PKC pathways can, possibly by different mechanisms, stimulate mRNA levels of the GtH II beta gene, but that only the cAMP-PKA pathway stimulates GH mRNA levels. It would appear therefore that GnRH, although stimulating GH release, does not regulate GH transcription in this fish.
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PMID:Differential effects of gonadotropin-releasing hormone, dopamine and somatostatin and their second messengers on the mRNA levels of gonadotropin II beta subunit and growth hormone in the teleost fish, tilapia. 889 62

Dopamine-somatostatin interactions were investigated in the rat striatum using in vivo microdialysis. Somatostatin-14 and somatostatin-28 (10(-4), 10(-5), 10(-6) M) were infused, and the levels of dopamine and its metabolites DOPAC and HVA were assessed using high pressure liquid chromatography with electrochemical detection. Somatostatin-14 was more effective than somatostatin-28 in producing a dose-dependent increase in dopamine levels with no significant alterations in the levels of the metabolites. To assess the effect of dopamine on somatostatinergic neurons, dopaminergic agents were administered and somatostatin levels measured using a radioimmunoassay. The nonselective agonist apomorphine was administered subcutaneously (0.00, 0.05, 0.10, 0.50, 1.00 mg/kg) or directly infused (10(-4), 10(-5) M) in the striatum. The selective D1 and D2 dopamine antagonists SCH23390 and sulpiride, respectively, were also infused at concentrations of 10(-4) and 10(-5) M. None of these agents elicited any significant changes in the somatostatin release in the striatum, while altering dopamine release. This study provides for the first time evidence regarding dopamine-somatostatin interactions in the awake and freely moving animal. The results confirm that somatostatin modulates the function of dopaminergic neurons in the striatum and provide new evidence that somatostatin-14 may differentially regulate dopamine release. Furthermore, our findings suggest that dopamine does not play a major role in the regulation of somatostatin neurons.
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PMID:Dopamine-somatostatin interactions in the rat striatum: an in vivo microdialysis study. 913 88

The effects of intra- and extra-adrenal peptides on [3H]dopamine uptake in adrenal chromaffin cells of the mouse were examined in vitro. Dopamine uptake was inhibited by acetylcholine, high potassium, reserpine, imipramine and desmethylimipramine as was in noradrenaline uptake. Among the intra-adrenal peptides, vasoactive intestinal peptide (VIP, 100 pmol/l) and neurotensin inhibited [3H]dopamine uptake by approximately 25%. Somatostatin, enkephalin, and neuropeptide Y did not cause any significant inhibition. An extra-adrenal peptide, bradykinin, inhibited the uptake while angiotensin II showed no significant effect. Intra-adrenal peptides which cause catecholamine secretion inhibit catecholamine uptake probably to extend its effect. Extra-adrenal peptide which causes catecholamine secretion also inhibits catecholamine uptake.
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PMID:Uptake of [3H]dopamine in isolated chromaffin cells of the mouse: modulation by intra- and extra-adrenal peptides and other secretagogues. 969 77

Management of pituitary tumors has improved in the past decade since the introduction of novel therapeutic agents. As a result, several treatment options are now available. Dopamine agonists are the preferred treatment for both symptomatic microprolactinomas and macroprolactinomas; these drugs result in normalization of hormone levels and tumor shrinkage in most treated patients. New formulations (such as cabergoline and parenteral bromocriptine) with prolonged duration of action offer improved compliance with treatment and cure rates. For acromegaly and adrenocorticotropin hormone (ACTH)-secreting, thyroid-stimulating hormone (TSH)-secreting, and nonfunctional adenomas, surgery often results in cure. Octreotide and the long-acting, slow-release somatostatin analogues are effective medical alternatives to or adjuvants for transsphenoidal surgery in patients with growth hormone-secreting and TSH-secreting tumors. No drug treatment is available for symptomatic nonfunctional tumors, and patients with ACTH-secreting adenomas may benefit from cortisol-lowering drugs after surgical failure. Pituitary irradiation may be required after surgery for ACTH-secreting, TSH-secreting, and nonfunctioning tumors; it is less commonly required for acromegaly. Although many pituitary tumors are successfully resected, functional adenomas may not be cured by surgery. As more-effective drugs are introduced for the management of pituitary tumors, more patients with hormone-secreting adenomas are being successfully treated medically.
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PMID:Management of pituitary tumors. 973 86

1. The neuroendocrine system of the lungs has no clear function. However, previous studies of one of its products, somatostatin, have implicated it in lung liquid removal at birth. The present study extends this concept by investigating the effects of dopamine, a major product of this system, on lung liquid reabsorption. 2. The effects of dopamine on fetal lung liquid production and reabsorption were tested on in vitro lungs from fetal guinea-pigs of 60 +/- 2 days of gestation (term = 67 days). Dopamine was placed in the outer bathing saline during the middle hour of 3 h incubations. Fluid movements across the pulmonary epithelium were monitored by a dye dilution method, and changes in rates over 1 h intervals were tested for significance by analysis of variance and regression analysis. 3. Dopamine was able to reduce fluid production or cause reabsorption (based on 42 preparations). Control preparations and those given 10-8 M dopamine showed no significant changes; those given higher concentrations showed significant reductions in production or reabsorption (P < 0.025 to P < 0.0005), according to dose (42.6 +/- 10.8% reduction at 10-7 M; 75.4 +/- 5.9% reduction at 10-6 M; 92.1 +/- 7.0% reduction at 10-5 M and 121.4 +/- 12.8% (reabsorption) at 10-4 M dopamine). The linear log dose-response curve (r = 0.99) showed a theoretical threshold at 1.7 x 10-9 M dopamine. 4. Effects were mediated through specific dopamine receptors (based on 78 preparations). Dopamine at 10-6 M was tested together with each of three dopamine receptor antagonists at 10-5 M. The general dopamine receptor antagonist haloperidol and the more specific D2 receptor blocker domperidone both abolished responses, but the D1 receptor antagonist SCH 23390 was without effect. This suggested that D2 dopamine receptors mediated the responses, and that responses were not due to conversion of dopamine to adrenaline or noradrenaline. 5. There was no evidence that responses involved amiloride-sensitive Na+ transport (based on 54 preparations). Apical amiloride at 10-6, 10-5 or 10-4 M, and the more specific Na+ channel blocker benzamil (10-5 M), had no effect on responses to dopamine, in contrast to their effects on responses to adrenaline in sheep. 6. It is suggested that internal release of dopamine by the neuroendocrine system of the lungs may influence lung liquid reabsorption at birth. This system, which also produces somatostatin, another agent active on lung liquid production, is maximally developed and activated at birth; it is also deficient in hyaline membrane disease.
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PMID:The effect of dopamine on lung liquid production by in vitro lungs from fetal guinea-pigs. 978 78

The pituitary of a number of teleosts contains two gonadotropins (GtHs) which are produced in distinct populations of cells; the beta subunit of the GtH I being found in close proximity to the somatotrophs, while the II beta cells are more peripheral. In several species the GtH beta subunits are expressed at varying levels throughout the reproductive cycle, the I beta dominating in early maturing fish, after which the II beta becomes predominant. This suggests differential control of the beta subunit synthesis which may be regulated by both hypothalamic hormones and gonadal steroids. At ovulation and spawning, changes also occur in the somatotrophs, which become markedly more active, while plasma growth hormone (GH) levels increase. In a number of species, GnRH elevates either the I beta or the II beta mRNA levels, depending on the reproductive state of the fish. In tilapia, the GnRH effect on the II beta appears to be mediated through both cAMP-PKA and PKC pathways. GnRH also stimulates GH release in both goldfish and tilapia, but it increases the GH transcript levels only in goldfish; both GnRH and direct activation of PKC are ineffective in altering GH mRNA in tilapia pituitary cells. Dopamine (DA) does not alter II beta transcript levels in cultured tilapia pituitary cells, but increases GH mRNA levels in both rainbow trout and tilapia, in a PKA-dependent manner. This effect appears to be through interactions with Pit-1 and also by stabilizing the mRNA. Somatostatin (SRIF) does not alter GH transcript levels in either tilapia or rainbow trout, although it may alter GH synthesis by modulation of translation. Gonadal steroids appear to have differential effects on the transcription of the beta subunits. In tilapia, testosterone (T) elevates I beta mRNA levels in cells from immature or early maturing fish (in low doses), but depresses them in cells from late maturing fish and is ineffective in cells from regressed fish. Similar results were seen in early recrudescing male coho salmon injected with T or E2. T or E2 administered in vivo has dramatic stimulatory effects on the II beta transcript levels in immature fish of a number of species, while less powerful effects are seen in vitro. A response is also seen in cells from early maturing rainbow trout or tilapia, or regressed tilapia, but not in cells from late maturing or spawning fish. These results are substantiated by the finding that the promoter of the salmon II beta gene contains several estrogen responsive elements (EREs) which react and interact differently when exposed to varying levels of E2. In addition, activator protein-1 (AP-1) and steroidogenic factor-1 (SF-1) response elements are also found in the salmon II beta promoter; the AP-1 site is located close to a half ERE, while the SF-1 acts synergistically with the E2 receptor. The mRNA levels of both AP-1 and SP-1 are elevated, at least in mammals, by GnRH, suggesting possible sites for cross-talk between GnRH and steroid activated pathways. Reports of the effects of T or E2 on GH transcription differ. No effect is seen in vitro in pituitaries of tilapia, juvenile rainbow trout or common carp, but T does increase the transcript levels in pituitaries of both immature and mature goldfish. Reasons for these discrepancies are unclear, but other systemic hormones may be more instrumental than the gonadal steroids in regulating GH transcription. These include T3 which increases both GH mRNA levels and de novo synthesis (in tilapia and common carp) and insulin-like growth factor-I (IGF-I) which reduces GH transcript levels as well as inhibiting GH release.
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PMID:Endocrine regulation of gonadotropin and growth hormone gene transcription in fish. 982 5

1 Somatostatin (SRIF) is a cyclic tetradecapeptide present in medium-sized aspiny interneurones in the rat striatum. We have previously shown that exogenous SRIF potently stimulates striatal dopamine (DA) release via a glutamate-dependent mechanism. We now report the ability of the selective sst2 receptor agonist, BIM-23027, to mimic this effect of SRIF. 2 In vivo microdialysis studies were performed in anaesthetized male Wistar rats. In most experiments, compounds were administered by retrodialysis into the striatum for 15 min periods, 90 min and 225 min after sampling commenced, with levels of neurotransmitters being measured by HPLC with electrochemical and fluorescence detection. 3 BIM-23027 (50 and 100 nM) stimulated DA release with extracellular levels increasing by up to 18 fold. 4 Prior retrodialysis of BIM-23027 (50 nM) abolished the effects of subsequent administration of SRIF (100 nM). 5 The agonist effects of both BIM-23027 and SRIF were abolished by the selective sst2 receptor antagonist, L-Tyr8-CYN-154806 (100 nM). 6 The AMPA/kainate receptor antagonist, DNQX (100 microM), abolished the agonist effects of BIM-23027 as previously shown for SRIF. 7 This study provides evidence that the sst2 receptor mediates the potent dopamine-releasing actions observed with SRIF in the rat striatum. Dopamine release evoked by both peptides appears to be mediated indirectly via a glutamatergic pathway. Other subtype-specific somatostatin receptor ligands were unable to elicit any effects and therefore we conclude that no other somatostatin receptor types are involved in mediating the dopamine-releasing actions of SRIF in the striatum.
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PMID:Evidence that somatostatin sst2 receptors mediate striatal dopamine release. 1057 51

Pituitary diseases are relatively common entities in the general population. They include pituitary adenomas and hypopituitarism. Pituitary tumours can cause symptoms of mass effect and hormonal hypersecretion that can be reversed with surgical resection or debulking of the adenoma, radiotherapy, or medical treatment. Transsphenoidal adenomectomy is the treatment of choice for acromegaly, Cushing's disease, gonadotropin-secreting tumours; and thyrotropin (TSH)-secreting adenomas. Pituitary irradiation and medical therapy are secondary options. Conversely, medical treatment is the primary choice for prolactinomas. Dopamine agonists are very effective in the treatment of prolactin (PRL)-secreting tumours, with rates of control as high as 80 to 90% for microprolactinomas (< 10 mm) and 60 to 75% for macroprolactinomas (> or = 10 mm). Somatostatin analogues have also shown efficacy in patients with acromegaly who have not responded to surgery or in patients with TSH-secreting adenomas who have not improved with surgery and radiotherapy. In patients with Cushing's disease, who are not cured surgically or who relapse after pituitary adenomectomy and irradiation, steroidogenic inhibitors can be an efficient method of controlling the hypercortisolism. Pituitary insufficiency is the partial or complete loss of the anterior hypophyseal function, which is due to hypothalamic or pituitary disease. Although the classic sequence of loss of pituitary secretion is growth hormone (GH), gonadotropins, TSH, and corticotropin (ACTH), the order to begin the replacement therapy of the deficient hormone(s) is cortisol, thyroxine, androgens/estrogens and, if necessary, GH. There are multiple preparations that can be used to achieve clinical and biochemical improvement. In general, the hormone replacement therapy is lifelong.
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PMID:Pituitary disorders. Drug treatment options. 1071 1


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